Skip to main content

Advertisement

SpringerLink
Log in

Serotonin pharmacology in the gastrointestinal tract: a review

  • Review
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Serotonin (5-hydroxytryptamine or 5-HT) plays a critical physiological role in the regulation of gastrointestinal (GI) function. 5-HT dysfunction may also be involved in the pathophysiology of a number of functional GI disorders, such as chronic constipation, irritable bowel syndrome and functional dyspepsia. This article describes the role of 5-HT in the enteric nervous system (ENS) of the mammalian GI tract and the receptors with which it interacts. Existing serotonergic therapies that have proven effective in the treatment of GI functional disorders and the potential of drugs currently in development are also highlighted. Advances in our understanding of the physiological and pathophysiological roles of 5-HT in the ENS and the identification of selective receptor ligands bodes well for the future development of more efficacious therapies for patients with functional GI disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aapro M (2005) 5-HT(3)-receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment. Oncology 69:97–109

    PubMed  CAS  Google Scholar 

  • Abell TL, Camilleri M, DiMagno EP, Hench VS, Zinsmeister AR, Malagelada JR (1991) Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility. Dig Dis Sci 36:616–620

    PubMed  CAS  Google Scholar 

  • Adham N, Kao HT, Schechter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA (1993) Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci USA 90:408–412

    PubMed  CAS  Google Scholar 

  • Alexander SPH, Mathie A, Peters JA (2004) Guide to receptors and channels. Br J Pharmacol 141(Suppl 1):S36–S37

    Google Scholar 

  • Alfieri AB, Cubeddu LX (1995) Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients. Br J Cancer 72:1013–1015

    PubMed  CAS  Google Scholar 

  • American Gastroenterological Association (2002) The burden of gastrointestinal diseases. American Gastroenterological Association, Bethesda, MD

    Google Scholar 

  • Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA (2006) Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome. Gastroenterology 130:34–43

    PubMed  CAS  Google Scholar 

  • Bacon WL, Beck SG (2000) 5-Hydroxytryptamine(7) receptor activation decreases slow afterhyperpolarization amplitude in CA3 hippocampal pyramidal cells. J Pharmacol Exp Ther 294:672–679

    PubMed  CAS  Google Scholar 

  • Bai F, Yin T, Johnstone EM, Su C, Varga G, Little SP, Nelson DL (2004) Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor. Eur J Pharmacol 484:127–139

    PubMed  CAS  Google Scholar 

  • Baker DE (2005) Rationale for using serotonergic agents to treat irritable bowel syndrome. Am J Health-Syst Pharm 62:700–711

    PubMed  Google Scholar 

  • Banh HL, MacLean C, Topp T, Hall R (2005) The use of tegaserod in critically ill patients with impaired gastric motility. Clin Pharmacol Ther 77:583–586

    PubMed  CAS  Google Scholar 

  • Banner SE, Sanger GJ (1995) Differences between 5-HT3 receptor antagonists in modulation of visceral hypersensitivity. Br J Pharmacol 114:558–562

    PubMed  CAS  Google Scholar 

  • Barbey JT, Lazzara R, Zipes DP (2002) Spontaneous adverse event reports of serious ventricular arrhythmias, QT prolongation, syncope, and sudden death in patients treated with cisapride. J Cardiovasc Pharmacol Ther 7:65–76

    PubMed  Google Scholar 

  • Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL (1993) Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem 268:23422–23426

    PubMed  CAS  Google Scholar 

  • Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152

    PubMed  CAS  Google Scholar 

  • Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PPA (2004) The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol 143:549–560

    PubMed  CAS  Google Scholar 

  • Beattie DT, Armstrong SR, Marquess D, Shaw J, Smith JA, Humphrey PP (2007) The in vivo preclinical profile of TD-5108, a selective, high intrinsic activity 5-HT4 receptor agonist. Digestive Disease Week, Washington, DC, W1228

  • Beique JC, Chapin-Pennick EM, Mladenovic L, Andrade R (2004) Serotonergic facilitation of synaptic activity in the developing rat prefrontal cortex. J Physiol 556:739–754

    PubMed  CAS  Google Scholar 

  • Bender E, Pindon A, Van Oers I, Zhang YB, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W (2000) Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. J Neurochem 74:478–489

    PubMed  CAS  Google Scholar 

  • Berman SM, Chang L, Suyenobu B, Derbyshire SW, Stains J, Fitzgerald L, Mandelkern M, Hamm L, Vogt B, Naliboff BD, Mayer EA (2002) Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist alosetron. Gastroenterology 123:969–977

    PubMed  CAS  Google Scholar 

  • Bertrand PP, Kunze WA, Furness JB, Bornstein JC (2000) The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors. Neuroscience 101:459–469

    PubMed  CAS  Google Scholar 

  • Bharucha AE, Camilleri M, Haydock S, Ferber I, Burton D, Cooper S, Tompson D, Fitzpatrick K, Higgins R, Zinsmeister AR (2000) Effects of a serotonin 5-HT4 receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans. Gut 47:667–674

    PubMed  CAS  Google Scholar 

  • Boeckxstaens GE, Tytgat GN, Wajs E, Van Nueten L, De Ridder F, Meulemans A, Tack J (2006) The influence of the novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers. Neurogastroenterol Motil 18:919–926

    PubMed  CAS  Google Scholar 

  • Bonaventure P, Nepomuceno D, Miller K, Chen J, Kuei C, Kamme F, Tran DT, Lovenberg TW, Liu C (2005) Molecular and pharmacological characterization of serotonin 5-HT2A and 5-HT2B receptor subtypes in dogs. Eur J Pharmacol 513:181–192

    PubMed  CAS  Google Scholar 

  • Borman RA, Burleigh DE (1995) Functional evidence for a 5-HT2B receptor mediating contraction of longitudinal muscle in human small intestine. Br J Pharmacol 114:1525–1527

    PubMed  CAS  Google Scholar 

  • Borman RA, Burleigh DE (1996) Human colonic mucosa possesses a mixed population of 5-HT receptors. Eur J Pharmacol 309:271–274

    PubMed  CAS  Google Scholar 

  • Borman RA, Burleigh DE (1997a) 5-HT1D and 5-HT2B receptors mediate contraction of smooth muscle in human small intestine. Ann NY Acad Sci 812:222–223

    PubMed  CAS  Google Scholar 

  • Borman RA, Burleigh DE (1997b) Heterogeneity of 5-HT receptors mediating secretion in the human intestine. Ann NY Acad Sci 812:224–225

    PubMed  CAS  Google Scholar 

  • Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, Baxter GS (2002) 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br J Pharmacol 135:1144–1151

    PubMed  CAS  Google Scholar 

  • Bouras EP, Camilleri M, Burton DD, McKinzie S (1999) Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut 44:682–686

    PubMed  CAS  Google Scholar 

  • Bradesi S, Lao L, McLean PG, Winchester WJ, Lee K, Hicks GA, Mayer EA (2007) Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia. Pain 130:56–65

    PubMed  CAS  Google Scholar 

  • Branchek TA, Mawe GM, Gershon MD (1988) Characterization and localization of a peripheral neural 5-hydroxytryptamine receptor subtype (5-HT1P) with a selective agonist, 3H-5-hydroxyindalpine. J Neurosci 8:2582–2595

    PubMed  CAS  Google Scholar 

  • Brattelid T, Kvingedal AM, Krobert KA, Andressen KW, Bach T, Hystad ME, Kaumann AJ, Levy FO (2004) Cloning, pharmacological characterisation and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i). Naunyn Schmiedeberg’s Arch Pharmacol 369:616–628

    CAS  Google Scholar 

  • Briejer MR, Akkermans LM, Schuurkes JA (1995a) Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon. Arch Int Pharmacodyn Ther 329:121–133

    PubMed  CAS  Google Scholar 

  • Briejer MR, Akkermans LMA, Schuurkes JAJ (1995b) Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev 47:631–651

    PubMed  CAS  Google Scholar 

  • Briejer MR, Bosmans JP, Van Daele P, Jurzak M, Heylen L, Leysen JE, Prins NH, Schuurkes JAJ (2001a) The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound. Eur J Pharmacol 423:71–83

    PubMed  CAS  Google Scholar 

  • Briejer MR, Prins NH, Schuurkes JA (2001b) Effects of the enterokinetic prucalopride (R093877) on colonic motility in fasted dogs. Neurogastroenterol Motil 13:465–472

    PubMed  CAS  Google Scholar 

  • Broekaert D, Fischler B, Sifrim D, Janssens J, Tack J (2006) Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal hypersensitivity: a double-blind, placebo-controlled study. Aliment Pharmacol Ther 23:365–370

    PubMed  CAS  Google Scholar 

  • Brown NJ, Horton A, Rumsey RD, Read NW (1993) Granisetron and ondansetron: effects on the ileal brake mechanism in the rat. J Pharm Pharmacol 45:521–524

    PubMed  CAS  Google Scholar 

  • Buchheit KH, Buhl T (1994) Stimulant effects of 5-hydroxytryptamine on guinea pig stomach preparations in vitro. Eur J Pharmacol 262:91–97

    Google Scholar 

  • Budhoo MR, Harris RP, Kellum JM (1996) 5-Hydroxytryptamine-induced Cl- transport is mediated by 5-HT3 and 5-HT4 receptors in the rat distal colon. Eur J Pharmacol 298:137–144

    PubMed  CAS  Google Scholar 

  • Calvert EL, Whorwell PJ, Houghton LA (2004) Inter-digestive and post-prandial antro-pyloro-duodenal motor activity in humans: effect of 5-hydroxytryptamine agonism. Aliment Pharmacol Ther 19:805–815

    PubMed  CAS  Google Scholar 

  • Camilleri M (2001) Review article: tegaserod. Aliment Pharmacol Ther 15:277–289

    PubMed  CAS  Google Scholar 

  • Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW (2000) Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 355:1035–1040

    PubMed  CAS  Google Scholar 

  • Camilleri M, Atanasova E, Carlson PJ, Ahmad U, Kim HJ, Viramontes BE, McKinzie S, Urrutia R (2002) Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 123:425–432

    PubMed  CAS  Google Scholar 

  • Camilleri M, McKinzie S, Fox J, Foxx-Orenstein A, Burton D, Thomforde G, Baxter K, Zinsmeister AR (2004) Effect of renzapride on transit in constipation-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2:895–904

    PubMed  CAS  Google Scholar 

  • Camilleri M, Burton D, Vasquez-Roque MI, Ford T, McKinzie S, Zinsmeister AR (2006) Effects of a novel 5-HT4 agonist, ATI-7505, on gastrointestinal and colonic transit in humans. Abstract T2029, Digestive Disease Week, Los Angeles, CA, May 20–25

  • Camilleri M, Andrews CN, Bharucha AE, Carlson PJ, Ferber I, Stephens D, Smyrk TC, Urrutia R, Aerssens J, Thielemans L, Gohlmann H, Van den Wyngaert I, Coulie B (2007) Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology 132:17–25

    PubMed  CAS  Google Scholar 

  • Carling RS, Degg TJ, Allen KR, Bax ND, Barth JH (2002) Evaluation of whole blood serotonin and plasma and urine 5-hydroxyindole acetic acid in diagnosis of carcinoid disease. Ann Clin Biochem 39:577–582

    PubMed  CAS  Google Scholar 

  • Carter D, Champney M, Hwang B, Eglen RM (1995) Characterization of a postjunctional 5-HT receptor mediating relaxation of guinea pig isolated ileum. Eur J Pharmacol 280:243–250

    PubMed  CAS  Google Scholar 

  • Cash BD, Chey WD (2005) Review article: the role of serotonergic agents in the treatment of patients with primary chronic constipation. Aliment Pharmacol Ther 22:1047–1060

    PubMed  CAS  Google Scholar 

  • Castro L, Mialet-Perez J, Guillemeau A, Stillitano F, Zolk O, Eschenhagen T, Lezoualch F, Bochet P, Fischmeister R (2005) Differential functional effects of two 5-HT4 receptor isoforms in adult cardiomyocytes. J Mol Cell Cardiol 39:335–344

    PubMed  CAS  Google Scholar 

  • Cellek S, John AK, Thangiah R, Dass NB, Bassil AK, Jarvie EM, Lalude O, Vivekanandan S, Sanger GJ (2006) 5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle. Neurogastroenterol Motil 18:853–861

    PubMed  CAS  Google Scholar 

  • Centurion D, Sanchez-Lopez A, Ortiz MI, De Vries P, Saxena PR, Villalon CM (2000) Mediation of 5-HT-induced internal carotid vasodilation in GR127935- and ritanserin-pretreated dogs by 5-HT7 receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 362:169–176

    CAS  Google Scholar 

  • Chang L, Chey W, Harris L, Olden K, Surawicz C, Schoenfeld P (2006) Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data. Am J Gastroenterol 101:1069–1079

    PubMed  Google Scholar 

  • Chen JJ, Zhishan L, Pan H, Murphy DL, Tamir H, Koepsell H, Gershon MD (2001) Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter (SERT): abnormal intestinal motility and the expression of cation transporters. J Neurosci 21:6348–6361

    PubMed  CAS  Google Scholar 

  • Chen JX, Pan H, Rowbotham TP, Wade PR, Gershon (1998) Guinea-pig 5-HT transporter: cloning, expression, distribution and function in intestinal sensory reception. Am J Physiol 275:G433–G448

    PubMed  CAS  Google Scholar 

  • Chey WD, Cash BD (2005) Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Exp Opin Invest Drugs 14:185–193

    CAS  Google Scholar 

  • Chial HJ, Camilleri M, Burton D, Thomforde G, Olden KW, Stephens D (2003a) Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health. Am J Physiol 284:G130–G137

    CAS  Google Scholar 

  • Chial HJ, Camilleri M, Ferber I, Delgado-Aros S, Burton D, McKinzie S, Zinsmeister AR (2003b) Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans. Clin Gastroenterol Hepatol 1:211–218

    PubMed  CAS  Google Scholar 

  • Claeysen S, Sebben M, Becamel C, Bockaert J, Dumuis A (1999) Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. Mol Pharmacol 55:910–920

    PubMed  CAS  Google Scholar 

  • Clayton NM, Sargent R, Butler A, Gale J, Maxwell MP, Hunt AA, Barrett VJ, Cambridge D, Bountra C, Humphrey PP (1999) The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat. Neurogastroenterol Motil 11:207–217

    PubMed  CAS  Google Scholar 

  • Clemens CHM, Samson M, Van Berge Henegouwen GP, Fabri M, Smout AJPM (2002) Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther 16:993–1002

    PubMed  CAS  Google Scholar 

  • Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, Crowell MD, Sharkey KA, Gershon MD, Mawe GM, Moses PL (2004) Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 126:1657–1664

    PubMed  CAS  Google Scholar 

  • Coates MD, Johnson AC, Greenwood-Van Meerveld B, Mawe GM (2006) Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse. Neurogastroenterol Motil 18:464–471

    PubMed  CAS  Google Scholar 

  • Cocks TM, Arnold PJ (1992) 5-Hydroxytryptamine (5-HT) mediates potent relaxation in the sheep isolated pulmonary vein via activation of 5-HT4 receptors. Br J Pharmacol 107:591–596

    PubMed  CAS  Google Scholar 

  • Coffin B, Farmachidi JP, Rueegg P, Bastie A, Bouhassira D (2003) Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects. Aliment Pharmacol Ther 17:577–585

    PubMed  CAS  Google Scholar 

  • Cole JA, Cook SF, Sands BE, Ajene AN, Miller DP, Walker AM (2004) Occurrence of colon ischemia in relation to irritable bowel syndrome. Am J Gastroenterol 99:486–491

    PubMed  Google Scholar 

  • Coleman NS, Marciani L, Blackshaw E, Wright J, Parker M, Yano T, Yamazaki S, Chan PQ, Wilde K, Gowland PA, Perkins AC, Spiller RC (2003) Effect of a novel 5-HT3 receptor agonist MKC-733 on upper gastrointestinal motility in humans. Aliment Pharmacol Ther 18:1039–1048

    PubMed  CAS  Google Scholar 

  • Cooke HJ, Sidhu M, Wang YZ (1997) Activation of 5-HT1P receptors on submucosal afferents subsequently triggers VIP neurons and chloride secretion in the guinea pig colon. J Auton Nerv Syst 66:105–110

    PubMed  CAS  Google Scholar 

  • Coremans G, Kerstens R, De Pauw M, Stevens M (2003) Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results from a double-blind, placebo-controlled clinical trial. Digestion 67:82–89

    PubMed  CAS  Google Scholar 

  • Costa M, Brookes SJH, Steele PA, Gibbins I, Burcher E, Kandiah CJ (1996) Neurochemical classification of myenteric neurons in the guinea pig ileum. Neuroscience 75:949–967

    PubMed  CAS  Google Scholar 

  • Costedio MM, Hyman N, Mawe GM (2007) Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum 50:376–388

    PubMed  Google Scholar 

  • Coulie B, Tack J, Maes B, Geypens B, De Roo M, Janssens J (1997) Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humans. Am J Physiol 272:G902–G908

    PubMed  CAS  Google Scholar 

  • Coulie B, Tack J, Sifrim D, Andrioli A, Janssens J (1999) Role of nitric oxide in fasting gastric fundus tone and in 5-HT1 receptor-mediated relaxation of gastric fundus. Am J Physiol 276:G373–377

    Google Scholar 

  • Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B (2003) The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 124:303–317

    PubMed  Google Scholar 

  • Cremonini F, Delgado-Aros S, Camilleri M (2003) Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials. Neurogastroenterol Motil 15:79–86

    PubMed  CAS  Google Scholar 

  • Croci T, Landi M, Bianchetti A, Manara L (1995) Drug-induced defaecation in rats: role of central 5-HT1A receptors. Br J Pharmacol 115:203–209

    PubMed  CAS  Google Scholar 

  • Cubeddu LX, Hoffman IS, Fuenmayor NT, Finn AL (1990) Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. New Eng J Med 322:810–816

    PubMed  CAS  Google Scholar 

  • Cuenca A, Liu MT, Holick K, Hen R, Gershon MD (2006) Physiological dependence of gastric emptying and intestinal motility on 5-HT4 receptors: analyses in wild-type and 5-HT4 knockout mice. Gastroenterology 130(Suppl S2):A5

    Google Scholar 

  • Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 397:359–363

    PubMed  CAS  Google Scholar 

  • Degen L, Matzinger D, Merz M, Appel-Dingemanse S, Osborne S, Luchinger S, Bertold R, Maecke H, Beglinger C (2001) Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects. Aliment Pharmacol Ther 15:1745–1751

    PubMed  CAS  Google Scholar 

  • Degen L, Petrig C, Studer D, Schroller S, Beglinger C (2005) Effect of tegaserod on gut transit in male and female subjects. Neurogastroenterol Motil 17:821–826

    PubMed  CAS  Google Scholar 

  • De Ponti F, Tonini M (2001) Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs 61:317–332

    PubMed  Google Scholar 

  • De Ponti F, Crema F, Moro E, Nardelli G, Frigo G, Crema A (2003) Role of 5-HT1B/D receptors in canine gastric accommodation: effect of sumatriptan and 5-HT1B/D receptor antagonists. Am J Physiol 285:G96–G104

    Google Scholar 

  • Deruyttere M, Lepoutre L, Heylen H, Samain H, Pennoit H (1987) Cisapride in the management of chronic functional dyspepsia: a multicenter, double-blind, placebo-controlled study. Clin Ther 10:44–51

    PubMed  CAS  Google Scholar 

  • Doggrell SA (2003) The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation. Expert Opin Invest Drugs 12:805–823

    CAS  Google Scholar 

  • Drici MD, Ebert SN, Wang WX, Rodriguez I, Liu XK, Whitfield BH, Woosley RL (1999) Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart. J Cardiovasc Pharmacol 34:82–88

    PubMed  CAS  Google Scholar 

  • Drossman DA (2006) The functional gastrointestinal disorders and the Rome III process. Gastroenterology 130:1377–1390

    PubMed  Google Scholar 

  • Dunlop SP, Coleman NS, Blackshaw E, Perkins AC, Singh G, Marsden CA, Spiller RC (2005) Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol 3:349–357

    PubMed  CAS  Google Scholar 

  • Ellis ES, Byrne C, Murphy OE, Tilford NS, Baxter GS (1995) Mediation by 5-hydroxytryptamine2B receptors of endothelium-dependent relaxation in rat jugular vein. Br J Pharmacol 114:400–404

    PubMed  CAS  Google Scholar 

  • Emmanuel AV, Kamm MA, Roy AJ, Antonelli K (1998) Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in healthy volunteers. Gut 42:511–516

    PubMed  CAS  Google Scholar 

  • Emmanuel AV, Roy AJ, Nicholls TJ, Kamm MA (2002) Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther 16:1347–1356

    PubMed  CAS  Google Scholar 

  • Engel L, Kobel B, Ontsouka EC, Graber HU, Blum JW, Steiner A, Meylan M (2006) Distribution of mRNA coding for 5-hydroxytryptamine receptor subtypes in the intestines of healthy dairy cows and dairy cows with cecal dilatation–dislocation. Am J Vet Res 67:95–101

    PubMed  CAS  Google Scholar 

  • Erspamer V, Vialli M (1937) Ricerche sul secreto delle cellule enterochromaffini. Boll Soc Med Chir Pavia 51:357–363

    Google Scholar 

  • Evangelista S (2007) Drug evaluation: Pumosetrag for the treatment of irritable bowel syndrome and gastroesophageal reflux disease. Curr Opin Invest Drugs 8:416–422

    CAS  Google Scholar 

  • Evans BW, Clark WK, Moore DJ, Whorwell PJ (2004) Tegaserod for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev 1:CD003960

    PubMed  Google Scholar 

  • Fiorica-Howells E, Maroteaux L, Gershon MD (2000) Serotonin and the 5-HT2B receptor in the development of enteric neurones. J Neurosci 20:294–305

    PubMed  CAS  Google Scholar 

  • Fiorica-Howells E, Hen R, Gingrich J, Li Z, Gershon MD (2002) 5-HT2A receptors: location and functional analysis in intestines of wild-type and 5-HT2A knockout mice. Am J Physiol 282:G877–G893

    CAS  Google Scholar 

  • Foguet M, Hoyer D, Pardo LA, Parekh A, Kluxen FW, Kalkman HO, Stühmer W, Lübbert H (1992) Cloning and functional characterization of the rat stomach fundus serotonin receptor. EMBO J 11:3481–3487

    PubMed  CAS  Google Scholar 

  • Foxx-Orenstein AE, Kuemmerle JF, Grider JR (1996) Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Gastroenterology 111:1281–1290

    PubMed  CAS  Google Scholar 

  • Freeman AJ, Cunningham KT, Tyers MB (1992) Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action. Anti-Cancer Drugs 3:79–85

    PubMed  CAS  Google Scholar 

  • Friedenberg FK, Parkman HP (2006) Delayed gastric emptying: whom to test, how to test, and what to do. Curr Treat Options Gastroenterol 9:295–304

    PubMed  Google Scholar 

  • Fujita T, Yokota S, Sawada M, Majima M, Ohtani Y, Kumagai Y (2005) Effect of MKC-733, a 5-HT receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study. J Clin Pharm Ther 30:611–622

    PubMed  CAS  Google Scholar 

  • Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP (1994) GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. Br J Pharmacol 111:332–338

    PubMed  CAS  Google Scholar 

  • Galligan JJ (1996) Electrophysiological studies of 5-hydroxytryptamine receptors on enteric neurons. Behav Brain Res 73:199–201

    PubMed  CAS  Google Scholar 

  • Galligan JJ (2002) Ligand-gated ion channels in the enteric nervous system. Neurogastroenterol Motil 14:611–623

    PubMed  CAS  Google Scholar 

  • Galligan JJ, LePard KJ, Schneider DA, Zhou X (2000) Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system. J Auton Nerv Syst 81:97–103

    PubMed  CAS  Google Scholar 

  • Galligan JJ, Pan H, Messori E (2003) Signalling mechanism coupled to 5-hydroxytryptamine4 receptor-mediated facilitation of fast synaptic transmission in the guinea pig ileum myenteric plexus. Neurogastroenterol Motil 15:523–529

    PubMed  CAS  Google Scholar 

  • Gallo-Torres H, Brinker A, Avigan M (2006) Alosetron: ischemic colitis and serious complications of constipation. Am J Gastroenterol 101:1080–1083

    PubMed  Google Scholar 

  • Galmiche JP, Clouse RE, Bálint A, Cook I, Kahrilas PJ, Paterson WG, Smout AJPM (2006) Functional esophageal disorders. Gastroenterol 130:1459–1465

    Google Scholar 

  • Gerald C, Adham N, Kao HT, Olsen MA, Laz TM, Schechter LE, Bard JA, Vaysse PJJ, Hartig PR (1995) The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 14:2806–2815

    PubMed  CAS  Google Scholar 

  • Gershon MD (2000) 5-HT (serotonin) physiology and related drugs. Curr Opin Gastroenterol 16:113–120

    PubMed  CAS  Google Scholar 

  • Gershon MD (2004) Review article: serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 20(Suppl 7):3–14

    PubMed  CAS  Google Scholar 

  • Gershon MD (2005) Nerves, reflexes, and the enteric nervous system. J Clin Gastroenterol 39:S184–S193

    PubMed  Google Scholar 

  • Gershon MD, Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterol 132:397–414

    CAS  Google Scholar 

  • Gerson L (2007) Comment. Gastroenterology 133:721–722

    Google Scholar 

  • Glatzle J, Sternini C, Robin C, Zittel TT, Wong H, Reeve JR, Raybould HE (2002) Expression of 5-HT3 receptors in the rat gastrointestinal tract. Gastroenterology 123:217–226

    PubMed  CAS  Google Scholar 

  • Goldberg MR, Wong SL, Ganju J, Li YP, Ballow CH, Kitt MM (2007a) TD-5108, a selective 5-HT4 agonist with high intrinsic activity, shows immediate and sustained prokinetic activity in healthy subjects. Abstract 318363, Digestive Disease Week, Washington, DC, May 19–24

  • Goldberg M, Li YP, Garofalo B, Valmonte A, Kitt M (2007b) TD-5108, a selective 5-HT4 agonist with high intrinsic activity, increases bowel movement frequency and provides significant overall relief in patients with chronic constipation. In: American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course, Philadelphia PA, October 12–17

  • Gorard DA, Libby GW, Farthing MJ (1994) 5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake. Gut 35:496–500

    PubMed  CAS  Google Scholar 

  • Gore S, Gilmore IT, Haigh CG, Brownless SM, Stockdale H, Morris AI (1990) Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther 4:139–144

    PubMed  CAS  Google Scholar 

  • Greenwood-Van Meerveld B, Campbell-Dittmeyer K, Johnson AC, Hicks GA (2006a) 5-HT2B receptors do not modulate sensitivity to colonic distension in rats with acute colorectal hypersensitivity. Neurogastroenterol Motil 18:343–345

    PubMed  CAS  Google Scholar 

  • Greenwood-Van Meerveld B, Venkova K, Hicks G, Dennis E, Crowell MD (2006b) Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension. Neurogastroenterol Motil 18:76–86

    PubMed  CAS  Google Scholar 

  • Grider JR (2003a) Reciprocal activity of longitudinal and circular muscle during intestinal peristaltic reflex. Am J Physiol Gastrointest Liver Physiol 284:G768–G775

    PubMed  CAS  Google Scholar 

  • Grider JR (2003b) Neurotransmitters mediating the intestinal peristaltic reflex in the mouse. J Pharmacol Exp Ther 307:460–467

    PubMed  CAS  Google Scholar 

  • Grider JR, Makhlouf GM (1990) Regulation of the peristaltic reflex by peptides of the myenteric plexus. Arch Int Pharmacodyn Ther 303:232–251

    PubMed  CAS  Google Scholar 

  • Grønstad KO, DeMagistris L, Dahlstrom A, Nilsson O, Price B, Zinner MJ, Jaffe BM, Ahlman H (1985) The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine. Scand J Gastroenterol 20:163–169

    PubMed  Google Scholar 

  • Haga K, Asano K, Fukuda T, Kobayakawa T (1995) The function of 5-HT3 receptors on colonic transit in rats. Obesity Res 3(Suppl 5):801S–810S

    CAS  Google Scholar 

  • Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (1992) Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity. Biochem Biophys Res Commun 184:752–759

    PubMed  CAS  Google Scholar 

  • Hansen MB, Skadhauge E (1997) Signal transduction pathways for serotonin as an intestinal secretagogue. Comp Biochem Physiol A Physiol 118:283–290

    PubMed  CAS  Google Scholar 

  • Hartig PR, Hoyer D, Humphrey PP, Martin GR (1996) Alignment of receptor nomenclature with the human genome classification of 5-HT1B and 5-HT1D receptor subtypes. Trends Pharmacol Sci 17:1003–1005

    Google Scholar 

  • Hawthorn J, Ostler KJ, Andrews PL (1988) The role of the abdominal visceral innervation and 5-hydroxytryptamine M-receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cis-platin in the ferret. Q J Exp Physiol 73:7–21

    PubMed  CAS  Google Scholar 

  • Hedlund PB, Danielson PE, Thomas EA, Slanina K, Carson MJ, Sutcliffe JG (2003) No hypothermic response to serotonin in 5-HT7 receptor knockout mice. Proc Natl Acad Sci USA 100:1375–1380

    PubMed  CAS  Google Scholar 

  • Hegde SS, Moy TM, Perry MR, Loeb M, Eglen RM (1994) Evidence for the involvement of 5-hydroxytryptamine 4 receptors in 5-hydroxytryptophan-induced diarrhea in mice. J Pharmacol Exp Ther 271:741–747

    CAS  Google Scholar 

  • Hesketh PJ (2004) Understanding the pathobiology of chemotherapy-induced nausea and vomiting. Providing a basis for therapeutic progress. Oncology 18(Suppl 6):9–14

    PubMed  Google Scholar 

  • Hicks GA, Clayton NM, Gaskin PJ, Kirkup AJ, Su X, Joshi S, Friedrich A, Conner HE, Cox B, Grundy D, Gebhart GF, Humphrey PPA (2001) 5-HT4 receptor agonists stimulate small intestinal transit but do not have direct visceral antinociceptive effects in the rat. Gastroenterology 120(Suppl 1):A–6

    Google Scholar 

  • Hofmann C, Penner U, Dorow R, Pertz HH, Jahnichen S, Horowski R, Latte KP, Palla D, Schurad B (2002) Lisuride a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis. Clin Neuropharmacol 29:80–86

    Google Scholar 

  • Horowski R, Jahnichen S, Pertz HH (2004) Fibrotic valvular heart disease is not related to chemical class but to biological function: 5-HT2B receptor activation plays crucial role. Mov Disord 19:1523–1524

    PubMed  Google Scholar 

  • Houghton LA, Jackson NA, Whorwell PJ, Cooper SM (1999) 5-HT4 receptor antagonism in irritable bowel syndrome: effect of SB-207266-A on rectal sensitivity and small bowel transit. Aliment Pharmacol Ther 13:1437–1444

    PubMed  CAS  Google Scholar 

  • Houghton LA, Foster JM, Whorwell PJ (2000) Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther 14:775–782

    PubMed  CAS  Google Scholar 

  • Houghton LA, Atkinson W, Whitaker RP, Whorwell PJ, Rimmer MJ (2003) Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome. Gut 52:663–670

    PubMed  CAS  Google Scholar 

  • Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203

    PubMed  CAS  Google Scholar 

  • Hoyer, D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    PubMed  CAS  Google Scholar 

  • Humphrey PP, Bountra C, Clayton N, Kozlowski K (1999) Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 13(Suppl 2):31–38

    PubMed  Google Scholar 

  • Imada-Shirakata Y, Kotera T, Ueda S, Okuma M (1997) Serotonin activates electrolyte transport via 5-HT2A receptor in rat colonic crypt cells. Biochem Biophys Res Commun 230:437–441

    PubMed  CAS  Google Scholar 

  • Irving HR, Tan YY, Tochon-Danguy N, Liu H, Chetty N, Desmond PV, Pouton CW, Coupar IM (2007) Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon. Life Sci 80:1198–1205

    PubMed  CAS  Google Scholar 

  • Ishida T, Kawashima S, Hirata K, Yokoyama M (1998) Nitric oxide is produced via 5-HT1B and 5-HT2B receptor activation in human coronary artery endothelial cells. Kobe J Med Sci 44:51–63

    PubMed  CAS  Google Scholar 

  • Ismair MG, Kullak-Ublick GA, Blakely RD, Fried M, Vavricka SR (2007) Tegaserod inhibits the serotonin transporter SERT. Digestion 75:90–95

    PubMed  CAS  Google Scholar 

  • Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L (2004) Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation. Circulation 110:969–974

    PubMed  Google Scholar 

  • James AN, Ryan JP, Parkman HP (2005) Effects of the selective serotonin reuptake inhibitor, fluoxetine, on regional gastric contractility. Neurogastroenterol Motil 17:76–82

    PubMed  CAS  Google Scholar 

  • Janssen P, Prins NH, Moreaux B, Meulemans AL, Lefebvre RA (2003) In vivo characterization of 5-HT1A receptor-mediated gastric relaxation in conscious dogs. Br J Pharmacol 140:913–920

    PubMed  CAS  Google Scholar 

  • Janssen P, Tack J, Sifrim D, Meulemans AL, Lefebvre RA (2004) Influence of 5-HT1 receptor agonists on feline stomach relaxation. Eur J Pharmacol 492:259–267

    PubMed  CAS  Google Scholar 

  • Jasper JR, Kosaka A, To ZP, Chang DJ, Eglen RM (1997) Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b). Br J Pharmacol 122:126–132

    PubMed  CAS  Google Scholar 

  • Jensen GM, Gronndahl ML, Nielsen CG, Skadhauge E, Olsen JE, Hansen MB (1997) Effect of ondansetron on Salmonella typhimurium-induced net fluid accumulation in the pig jejunum in vivo. Comp Biochem Physiol 118:297–299

    CAS  Google Scholar 

  • Jiang W, Kreis ME, Eastwood C, Kirkup AJ, Humphrey PP, Grundy D (2000) 5-HT(3) and histamine H(1) receptors mediate afferent nerve sensitivity to intestinal anaphylaxis in rats. Gastroenterol 119:1267–1275

    CAS  Google Scholar 

  • Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AMV, Rozmahel R, Yang Y, Mengod G, Palacios JM, O’Dowd BF (1992) Characterization of the human 5-hydroxytryptamine1B receptor. J Biol Chem 267:5735–5738

    PubMed  CAS  Google Scholar 

  • Jin JG, Foxx-Orenstein AE, Grider JR (1999) Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors. J Pharmacol Exp Ther 288:93–97

    PubMed  CAS  Google Scholar 

  • Johanson JF (2004) Review article: tegaserod for chronic constipation. Aliment Pharmacol Ther 20(Suppl 7):20–24

    PubMed  CAS  Google Scholar 

  • Jones BJ, Blackburn TP (2002) The medical benefit of 5-HT research. Pharmacol Biochem Behav 71:555–568

    PubMed  CAS  Google Scholar 

  • Jordan D (2005) Vagal control of the heart: central serotonergic (5-HT) mechanisms. Exp Physiol 90:175–181

    PubMed  CAS  Google Scholar 

  • Kahrilas PJ, Quigley EMM, Castell DO, Spechler SJ (2000) The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 14:1503–1509

    PubMed  CAS  Google Scholar 

  • Kajita S, Ito C, Kawamura R, Yasuda S, Isobe Y, Fukushima K (2001) Pharmacological characterization of a novel 5-HT4 receptor agonist, TS-951, in vitro. Pharmacology 63:8–16

    PubMed  CAS  Google Scholar 

  • Kamm MA (2002) Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther 16:343–351

    PubMed  CAS  Google Scholar 

  • Kaumann AJ, Levy FO (2006) 5-hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther 111:674–706

    PubMed  CAS  Google Scholar 

  • Kellum JM, Budhoo MR, Siriwardena AK, Smith EP, Jebraili SA (1994) Serotonin induces Cl- secretion in human jejunal mucosa in vitro via a nonneural pathway at a 5-HT4 receptor. Am J Physiol 267:G357–G363

    PubMed  CAS  Google Scholar 

  • Kilkens TOC, Honig A, Van Niewenhoven MA, Riedel WJ, Brummer RJM (2004) Acute tryptophan depletion affects brain–gut responses in irritable bowel syndrome patients and controls. Gut 53:1794–1800

    PubMed  CAS  Google Scholar 

  • Kim DY, Camilleri M (2000) Serotonin: a mediator of the brain–gut connection. Am J Gastroenterol 95:2698–2709

    PubMed  CAS  Google Scholar 

  • Kirchgessner AL, Liu MT, Howard MJ, Gershon MD (1993) Detection of the 5-HT1A receptor and 5-HT1A receptor mRNA in the rat bowel and pancreas: comparison with 5-HT1P receptors. J Comp Neurol 327:233–250

    PubMed  CAS  Google Scholar 

  • Kirchgessner AL, Liu MT, Raymond JR, Gershon MD (1996) Identification of cells that express 5-hydroxytryptamine 1A receptors in the nervous systems of the bowel and pancreas. J Comp Neurol 364:439–455

    PubMed  CAS  Google Scholar 

  • Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW (1996) Cloning, characterization and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem 66:47–56

    PubMed  CAS  Google Scholar 

  • Komada T, Yano S (2007) Pharmacological characterization of 5-Hydroxytryptamine-receptor subtypes in circular muscle from the rat stomach. Biol Pharm Bull 30:508–513

    PubMed  CAS  Google Scholar 

  • Kozlowski CM, Green A, Grundy D, Boissonade FM, Bountra C (2000) The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distension induced depressor response and spinal c-fos expression in the anaesthetised rat. Gut 46:474–480

    PubMed  CAS  Google Scholar 

  • Krobert KA, Bach T, Syversveen T, Kvingedal AM, Levy FO (2001) The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution. Naunyn-Schmiedeberg’s Arch Pharmacol 363:620–632

    CAS  Google Scholar 

  • Kuemmerle JF, Murthy KS, Grider JR, Martin DC, Makhlouf GM (1995) Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells. Gastroenterology 109:1791–1800

    PubMed  CAS  Google Scholar 

  • Kuiken SD, Tytgat GN, Boeckxstaens GE (2003) The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clin Gastroenterol Hepatol 1:219–228

    PubMed  CAS  Google Scholar 

  • Kuo B, Camilleri M, Burton D, Viramontes B, McKinzie S, Thomforde G, O’Connor MK, Brinkmann BH (2002) Effects of 5-HT3 antagonism on postprandial gastric volume and symptoms in humans. Aliment Pharmacol Ther 16:225–233

    PubMed  CAS  Google Scholar 

  • Kursar JD, Nelson DL, Wainscott DB, Baez M (1994) Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor. Mol Pharmacol 46:227–234

    PubMed  CAS  Google Scholar 

  • Ladabaum U, Glidden D (2002) Effect of the selective serotonin reuptake inhibitor sertraline on gastric sensitivity and compliance in healthy humans. Neurogastroenterol Motil 14:395–402

    PubMed  CAS  Google Scholar 

  • Lea R, Houghton LA, Whorwell PJ, Whitaker RP (2002) Evidence for increased plasma 5-hydroxytryptamine (5-HT) concentration following meal ingestion in patients with functional dyspepsia (FD) and its relationship to gender and symptoms. Gastroenterology 122:304

    Google Scholar 

  • Leclere PG, Prins NH, Schuurkes JA, Lefebvre RA (2005) 5-HT4 receptors located on cholinergic nerves in human colon circular muscle. Neurogastroenterol Motil 17:366–375

    PubMed  CAS  Google Scholar 

  • Leysen JE (2004) 5-HT(2) receptors. Curr Drug Target CNS Neurol Disord 3:11–26

    CAS  Google Scholar 

  • Liu M, Gershon MD (2005b) Slow excitatory (‘5-HT1P’-like) responses of mouse myenteric neurons to 5-HT: mediation by heterodimers of 5-HT1B/1D and Drd2 receptors. Gastroenterology 128(4 Suppl 2):A87

    Google Scholar 

  • Liu M, Geddis MS, Wen Y, Setlik W, Gershon MD (2005a) Expression and function of 5-HT4 receptors in the mouse enteric nervous system. Am J Physiol 289:G1148–G1163

    CAS  Google Scholar 

  • Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491

    PubMed  Google Scholar 

  • Mackie AD, Ferrington C, Cowan S, Merrick MV, Baird JD, Palmer KR (1991) The effect of renzapride, a novel prokinetic agent, in diabetic gastroparesis. Aliment Pharmacol Ther 5:135–142

    PubMed  CAS  Google Scholar 

  • Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D (1991) Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254:432–437

    PubMed  CAS  Google Scholar 

  • Martel F (2006) Recent advances on the importance of the serotonin transporter SERT in the rat intestine. Pharmacol Res 54:73–76

    PubMed  CAS  Google Scholar 

  • Martel F, Monteiro R, Lemos C (2003) Uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells occurs through the neuronal serotonin transporter (SERT). J Pharmacol Exp Ther 306:355–362

    PubMed  CAS  Google Scholar 

  • Mawe GM, Branchek TA, Gershon MD (1986) Peripheral neural serotonin receptors: Identification and characterization with specific antagonists and agonists. Proc Natl Acad Sci USA 83:9799–9803

    PubMed  CAS  Google Scholar 

  • Mawe GM, Coates MD, Moses PL (2006) Review article: intestinal serotonin signalling in irritable bowel syndrome. Aliment Pharmacol Ther 23:1067–1076

    PubMed  CAS  Google Scholar 

  • Mayer EA, Bradesi S (2003) Alosetron and irritable bowel syndrome. Exp Opin Pharmacother 4:2089–2098

    CAS  Google Scholar 

  • Mayer EA, Berman S, Derbyshire SWG, Suyenobu B, Chang L, Fitzgerald L, Manelkern M, Hamm L, Vogt B, Naliboff BD (2002) The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Aliment Pharmacol Ther 16:1357–1366

    PubMed  CAS  Google Scholar 

  • McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P (1992) Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype. Proc Natl Acad Sci USA 89:5517–5521

    PubMed  CAS  Google Scholar 

  • McNulty R (2007) Are all 5-HT3 receptor antagonists the same? J Natl Comp Cancer Netw 5:35–43

    CAS  Google Scholar 

  • Medhurst AD, Lezoualch F, Fischmeister R, Middlemiss DN, Sanger GJ (2001) Quantitative mRNA analysis of five C-terminal splice variants of the human 5-HT4 receptor in the central nervous system by TaqMan real time RT-PCR. Brain Res Mol Brain Res 90:125–134

    PubMed  CAS  Google Scholar 

  • Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA (1998) Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am J Gastroenterol 93:160–165

    PubMed  CAS  Google Scholar 

  • Meyers NL, Hickling RI (2007) The cardiovascular safety profile of renzapride, a novel treatment for irritable bowel syndrome. J Int Med Res 35:848–866

    PubMed  CAS  Google Scholar 

  • Mialet J, Fischmeister R, Lezoualch F (2003) Characterization of human 5-HT4(d) receptor desensitization in CHO cells. Br J Pharmacol 138:445–452

    PubMed  CAS  Google Scholar 

  • Mir AK, Hibert M, Tricklebank MD, Middlemiss DN, Kidd EJ, Fozard JR (1988) MDL 72832: a potent and stereoselective ligand at central and peripheral 5-HT1A receptors. Eur J Pharmacol 149:107–120

    PubMed  CAS  Google Scholar 

  • Mitchell ES, Neumaier JF (2005) 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacol Ther 108:320–333

    PubMed  CAS  Google Scholar 

  • Monro RL, Bornstein JC, Bertrand PP (2005) Slow excitatory post-synaptic potentials in myenteric AH neurons of the guinea pig ileum are reduced by the 5-hydroxytryptamine(7) receptor antagonist SB 269970. Neuroscience 134:975–986

    PubMed  CAS  Google Scholar 

  • Mori T, Kawano K, Shishikura T (2004) 5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats. J Pharmacol Sci 94:73–76

    PubMed  CAS  Google Scholar 

  • Morteau O, Julia V, Eeckhout C, Bueno L (1994) Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats. Fundam Clin Pharmacol 8:553–562

    Article  PubMed  CAS  Google Scholar 

  • Muller-Lissner SA (1987) Treatment of chronic constipation with cisapride and placebo. Gut 28:1033–1038

    PubMed  CAS  Google Scholar 

  • Muller-Lissner SA, Fumagalli I, Bardhan KD, Pace F, Pecher E, Nault B, Ruegg P (2001) Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 15:1655–1666

    PubMed  CAS  Google Scholar 

  • Nagakura Y, Kamato T, Nishida A, Ito H, Yamano M, Miyata K (1996a) Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs. Naunyn-Schmiedeberg’s Arch Pharmacol 353:489–498

    CAS  Google Scholar 

  • Nagakura Y, Naitoh Y, Kamato T, Yamano M, Miyata K (1996b) Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice. Eur J Pharmacol 311:67–72

    PubMed  CAS  Google Scholar 

  • Navari RM (2006) Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol 2:591–602

    PubMed  CAS  Google Scholar 

  • Nebigil CG, Maroteaux L (2003) Functional consequences of serotonin/5-HT2B receptor signaling in heart. Circulation 108:902–908

    PubMed  Google Scholar 

  • Nebigil CG, Launay JM, Hickel P, Tournois C, Maroteaux L (2000) 5-Hydroxytryptamine 2B receptor regulates cell-cycle progression: cross-talk with tyrosine kinase pathways. Proc Natl Acad Sci USA 97:2591–2596

    PubMed  CAS  Google Scholar 

  • Nelson D (2004) 5-HT5 receptors. Curr Drug Targets 3:53–58

    CAS  Google Scholar 

  • Nicholson R, Small J, Dixon AK, Spanswick D, Lee K (2003) Serotonin receptor mRNA in dorsal root ganglion neurons. Neurosci Lett 337:119–122

    PubMed  CAS  Google Scholar 

  • Niesler B, Frank B, Kapeller J, Rappold GA (2003) Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene 310:101–111

    PubMed  CAS  Google Scholar 

  • Nilsson T, Longmore J, Shaw D, Pantev E, Bard JA, Branchek T, Edvinsson L (1999) Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. Eur J Pharmacol 372:49–56

    PubMed  CAS  Google Scholar 

  • Ning Y, Zhu JX, Chan HC (2004) Regulation of ion transport by 5-hydroxytryptamine in rat colon. Clin Exp Pharmacol Physiol 31:424–428

    PubMed  CAS  Google Scholar 

  • Pan H, Galligan JJ (1994) 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. Am J Physiol 266:G230–G238

    PubMed  CAS  Google Scholar 

  • Pan H, Gershon MD (2000) Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J Neurosci 20:3295–3309

    PubMed  CAS  Google Scholar 

  • Parkman HP, Hasler WL, Fisher RS (2004) American gastroenterological association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 127:1592–1622

    PubMed  Google Scholar 

  • Pascual D, Alsasua A, Goicoechea C, Martin MI (2002) The involvement of 5-HT3 and 5-HT4 receptors in two models of gastrointestinal transit in mice. Neurosci Lett 326:163–166

    PubMed  CAS  Google Scholar 

  • Pasricha PJ (2007) Desperately seeking serotonin…a commentary on the withdrawal of tegaserod and the state of drug development for functional and motility disorders. Gastroenterology 132:2287–2290

    PubMed  Google Scholar 

  • Pierce PA, Xie GX, Levine JD, Peroutka SJ (1996) 5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: a polymerase chain reaction study. Neuroscience 70:553–559

    PubMed  CAS  Google Scholar 

  • Pierce PA, Xie GX, Meuser T, Peroutka SJ (1997) 5-Hydroxytryptamine receptor subtype messenger RNAs in human dorsal root ganglia: a polymerase chain reaction study. Neuroscience 81:813–819

    PubMed  CAS  Google Scholar 

  • Pindon A, Van Hecke G, Van Gompel P, Lesage AS, Leysen JE, Jurzak M (2002) Differences in signal transduction of two 5-HT4 receptor splice variants: compound specificity and dual coupling with Galphas- and Galphai/o-proteins. Mol Pharmacol 61:85–96

    PubMed  CAS  Google Scholar 

  • Poen AC, Felt-Bersma RJF, Van Dongen PAM, Meuwissen SGM (1999) Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers. Aliment Pharmacol Ther 13:1493–1497

    PubMed  CAS  Google Scholar 

  • Ponimaskin EG, Heine M, Joubert L, Sebben M, Bickmeyer U, Richter DW, Dumuis A (2002) The 5-hydroxytryptamine(4a) receptor is palmitoylated at two different sites, and acylation is critically involved in regulation of receptor constitutive activity. J Biol Chem 277:2534–2546

    PubMed  CAS  Google Scholar 

  • Poole DP, Xu B, Koh SL, Hunne B, Coupar IM, Irving HR, Shinjo K, Furness JB (2006) Identification of neurons that express 5-hydroxytryptamine4 receptors in intestine. Cell Tissue Res 325:413–422

    PubMed  CAS  Google Scholar 

  • Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde G (2000) Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 118:463–468

    PubMed  CAS  Google Scholar 

  • Prins NH, Briejer MR, Schuurkes JA (1997) Characterization of the contraction to 5-HT in the canine colon longitudinal muscle. Br J Pharmacol 120:714–720

    PubMed  CAS  Google Scholar 

  • Prins NH, Briejer MR, Van Bergen PJ, Akkermans LM, Schuurkes JA (1999a) Evidence for 5-HT7 receptors mediating relaxation of human colonic circular smooth muscle. Br J Pharmacol 128:849–852

    PubMed  CAS  Google Scholar 

  • Prins NH, Van Haselen JF, Lefebvre RA, Briejer MR, Akkermans LM, Schuurkes JA (1999b) Pharmacological characterization of 5-HT4 receptors mediating relaxation of canine isolated rectum circular smooth muscle. Br J Pharmacol 127:1431–1437

    PubMed  CAS  Google Scholar 

  • Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 90:2542–2546

    PubMed  CAS  Google Scholar 

  • Raybould HE, Glatzle J, Robin C, Meyer JH, Phan T, Wong H, Sternini C (2003) Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying. Am J Physiol 284:G367–G372

    CAS  Google Scholar 

  • Read NM, Gwee KA (1994) The importance of 5-hydroxytryptamine receptors in the gut. Pharmacol Ther 62:159–173

    PubMed  CAS  Google Scholar 

  • Reeves JJ, Bunce KT, Humphrey PP (1991) Investigation into the 5-hydroxytryptamine receptor mediating smooth muscle relaxation in the rat oesophagus. Br J Pharmacol 103:1067–1072

    PubMed  CAS  Google Scholar 

  • Rizzi CA, Sagrada A, Schiavone A, Schiantarelli P, Cesana R, Schiavi GB, Ladinsky H, Donetti A (1994) Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 349:338–345

    CAS  Google Scholar 

  • Rodriguez-Stanley S, Zubaidi S, Proskin HM, Kralstein JR, Shetzline MA, Miner PB, Philip B (2006) Effect of tegaserod on esophageal pain threshold, regurgitation, and symptom relief in patients with functional heartburn and mechanical sensitivity. Clin Gastroenterol Hepatol 4:442–450

    PubMed  CAS  Google Scholar 

  • Roila F, Fatigoni S (2006) New antiemetic drugs. Ann Oncol 17(Suppl 2):96–100

    Google Scholar 

  • Ruat M, Traiffort E, Arrang JM, Tardivellacombe J, Diaz J, Leurs R, Schwartz JC (1993) A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation. Biochem Biophys Res Commun 193:268–276

    PubMed  CAS  Google Scholar 

  • Rubenstein EB (2004) Palonosetron: a unique 5-HT(3) receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol 2:284–288

    PubMed  Google Scholar 

  • Saad RJ, Chey WD (2006) Review article: current and emerging therapies for functional dyspepsia. Aliment Pharmacol Ther 24:475–492

    PubMed  CAS  Google Scholar 

  • Säfsten B, Sjöblom M, Flemström G (2006) Serotonin increases protective duodenal bicarbonate secretion via enteric ganglia and a 5-HT4-dependent pathway. Scand J Gastroenterol 41:1279–1289

    PubMed  Google Scholar 

  • Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S (1991) Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun 181:1469–1478

    PubMed  CAS  Google Scholar 

  • Sanger GJ, Andrews PLR (2006) Treatment of nausea and vomiting: gaps in our knowledge. Autonom Neurosci Basic Clin 129:3–16

    CAS  Google Scholar 

  • Sanger GJ, Wardle KA (1994) Constipation evoked by 5-HT3-receptor antagonism: evidence for heterogeneous efficacy among different antagonists in guinea pigs. J Pharm Pharmacol 46:666–670

    PubMed  CAS  Google Scholar 

  • Sanger GJ, Banner SE, Smith MI, Wardle KA (1998) SB-207266: 5-HT4 receptor antagonism in human isolated gut and prevention of 5-HT-evoked sensitization of peristalsis and increased defaecation in animal models. Neurogastroenterol Motil 10:271–279

    PubMed  CAS  Google Scholar 

  • Schoeffter P, Hoyer D (1990) 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther 252:387–395

    PubMed  CAS  Google Scholar 

  • Schworer H, Ramadori G (1998) Autoreceptors can modulate 5-hydroxytryptamine release from porcine and human small intestine in vitro. Naunyn-Schmiedeberg’s Arch Pharmacol 357:548–552

    CAS  Google Scholar 

  • Shen Y, Monsma FJ, Metcalf MA, Jose PA, Hamblin MW, Sibley DR (1993) Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem 268:18200–18204

    PubMed  CAS  Google Scholar 

  • Shufflebotham J, Hood S, Hendry J, Hince DA, Morris K, Nutt D, Probert C, Potokar J (2006) Acute tryptophan depletion alters gastrointestinal and anxiety symptoms in irritable bowel syndrome. Am J Gastroenterol 101:2582–2587

    PubMed  CAS  Google Scholar 

  • Sifrim D, Holloway RH, Tack J, Zelter A, Missotten T, Coulie B, Janssens J (1999) Effect of sumatriptan, a 5-HT1 agonist, on the frequency of transient lower esophageal sphincter relaxations and gastroesophageal reflux in healthy subjects. Am J Gastroenterol 94:3158–3164

    PubMed  CAS  Google Scholar 

  • Sivarao DV, Newberry K, Lodge NJ (2004) Effect of the 5-HT1A receptor partial agonist buspirone on colorectal distension-induced pseudoaffective and behavioral responses in the female Wistar rat. Eur J Pharmacol 494:23–29

    PubMed  CAS  Google Scholar 

  • Sloots CE, Poen AC, Kerstens R, Stevens M, De Pauw M, Van Oene JC, Meuwissen SG, Felt-Bersma RJ (2002) Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation. Aliment Pharmacol Ther 16:759–767

    PubMed  CAS  Google Scholar 

  • Smith JA, Beattie DT, Cuthbert AW, Ropenga A, Marquess D, Shaw J, Vickery R, Humphrey PP (2007) TD-5108, a selective, high intrinsic activity 5-HT4 receptor agonist - in vitro profile at human recombinant 5-HT4 receptor splice variant and human isolated colon. Digestive Disease Week, Washington, DC, W1222

  • Spigset O (1999) Adverse reactions of selective reuptake inhibitors: reports from a spontaneous reporting system. Drug Saf 20:277–287

    PubMed  CAS  Google Scholar 

  • Stacher G, Weber U, Stacher-Janotta G, Bauer P, Huber K, Holzapfel A, Krause G, Steinborn C (2000) Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial. Br J Clin Pharmacol 49:429–436

    PubMed  CAS  Google Scholar 

  • Sun YN, Luo JY (2004) Effects of tegaserod on Fos, substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord. World J Gastroenterol 10:1830–1833

    PubMed  CAS  Google Scholar 

  • Tack J, Janssens J, Vantrappen G, Wood JD (1992) Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum. Am J Physiol 263:G838–G846

    PubMed  CAS  Google Scholar 

  • Tack J, Coulie B, Wilmer A, Andrioli A, Janssens J (2000) Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man. Gut 46:468–473

    PubMed  CAS  Google Scholar 

  • Tack J, Bisschops R, DeMarchi B (2001) Causes and treatment of functional dyspepsia. Curr Gastroenterol Rep 3:503–508

    PubMed  CAS  Google Scholar 

  • Tack J, Van Elzen B, Tytgat G (2004) A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia. Gastroenterology 126:A70

    Google Scholar 

  • Tack J, Broekaert D, Corsetti M, Fischler B, Janssens J (2006a) Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man. Aliment Pharmacol Ther 23:265–274

    PubMed  CAS  Google Scholar 

  • Tack J, Middleton SJ, Horne MC, Piessevaux H, Bloor JS, Meyers NL (2006b) Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol Ther 23:1655–1665

    PubMed  CAS  Google Scholar 

  • Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada J-R, Stanghellini V (2006c) Functional gastroduodenal disorders. Gastroenterology 130:1466–1479

    PubMed  Google Scholar 

  • Tack J, Vanden Berghe P, Coulie B, Janssens J (2007) Sumatriptan is an agonist at 5-HT receptors on myenteric neurones in the guinea-pig gastric antrum. Neurogastroenterol Motil 19:39–46

    PubMed  CAS  Google Scholar 

  • Takayanagi S, Hanai H, Kumagai J, Kaneko E (1995) Serotonin uptake and its modulation in rat jejunal enterocyte preparation. J Pharmacol Exp Ther 272:1151–1159

    PubMed  CAS  Google Scholar 

  • Talley NJ (2003a) Update on the role of drug therapy in non-ulcer dyspepsia. Rev Gastroenterol Disord 3:25–30

    PubMed  Google Scholar 

  • Talley NJ (2003b) Pharmacologic therapy for the irritable bowel syndrome. Am J Gastroenterol 98:750–758

    PubMed  CAS  Google Scholar 

  • Talley NJ (2004) Antidepressants in IBS: are we deluding ourselves? Am J Gastroenterol 99:921–923

    PubMed  Google Scholar 

  • Tamaoki S, Yamauchi Y, Nakano Y, Sakano S, Asagarasu A, Sato M (2007) Pharmacological properties of 3-amino-5,6,7,8-tetrahydro-2-[4-[4-(quinolin-2-yl)piperazin-1-yl]butyl]quinazolin-4(3H)-one (TZB-30878), a novel therapeutic agent for diarrhea-predominant irritable bowel syndrome (IBS) and its effects on an experimental IBS model. J Pharmacol Exp Ther 322:1315–1323

    PubMed  CAS  Google Scholar 

  • Tam FS, Hillier K, Bunce KT (1994) Characterization of the 5-hydroxytryptamine receptor type involved in inhibition of spontaneous activity of human isolated colonic circular muscle. Br J Pharmacol 113:143–150

    PubMed  CAS  Google Scholar 

  • Tamura T, Sano I, Satoh M, Mizumoto A, Itoh Z (1996) Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus. Eur J Pharmacol 308:315–324

    PubMed  CAS  Google Scholar 

  • Taniyama K, Nakayama S, Takeda K, Matsuyama S, Shirakawa J, Sano I, Tanaka C (1991) Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors. J Pharmacol Exp Ther 258:1098–1104

    PubMed  CAS  Google Scholar 

  • Taniyama K, Makimoto N, Furuichi A, Sakurai-Yamashita Y, Nagase Y, Kaibara M, Kanematsu T (2000) Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility. J Gastroenterol 35:575–582

    PubMed  CAS  Google Scholar 

  • Tonini M (2005) 5-Hydroxytryptamine effects in the gut: the 3, 4, and 7 receptors. Neurogastroenterol Motil 17:637–642

    PubMed  CAS  Google Scholar 

  • Tonini M, De Ponti F, Di Nucci A, Crema F (1999) Review article: cardiac adverse effects of gastrointestinal prokinetics. Aliment Pharmacol Ther 13:1585–1591

    PubMed  CAS  Google Scholar 

  • Tonini M, Vicini R, Cervio E, De Ponti F, De Giorgio R, Barbara G, Stanghellini V, Dellabianca A, Sterini C (2005) 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum. Gastroenterology 129:1557–1566

    PubMed  CAS  Google Scholar 

  • Tsou AP, Kosaka A, Bach C, Zuppan P, Yee C, Tom L, Alvarez R, Ramsey S, Bonhaus DW, Stefanich E, Jakeman L, Eglen RM, Chan HW (1994) Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to adenylyl cyclase. J Neurochem 63:456–464

    Article  PubMed  CAS  Google Scholar 

  • Tyers MB, Freeman AJ (2002) Mechanism of the anti-emetic activity of 5-HT3 receptor antagonists. Oncology 49:263–268

    Google Scholar 

  • Tzvetkov MV, Meineke C, Oetjen E, Hirsch-Ernst K, Brockmoller J (2007) Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine. Gene 386:52–62

    PubMed  CAS  Google Scholar 

  • Vane JR (1957) A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol 12:344–349

    CAS  Google Scholar 

  • Vanhoenacker P, Haegeman G, Leysen JE (2000) 5-HT7 receptors: current knowledge and future prospect. Trends Pharmacol Sci 21:70–77

    PubMed  CAS  Google Scholar 

  • Van Lelyveld N, Ter Linde J, Baron A, Mundt M, Wajs E, Samsom M (2006) The 5-HT4 antagonist R216073 does not affect gastric motor and sensory function in patients with functional dyspepsia. Aliment Pharmacol Ther 24:669–677

    PubMed  Google Scholar 

  • Van Lelyveld N, Ter Linde J, Schipper ME, Samsom M (2007) Regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the human stomach and duodenum. Neurogastroenterol Motil 19:342–348

    PubMed  Google Scholar 

  • Veldhuyzen van Zanten SJO, Jones MJ, Verlinden M, Talley NJ (2001) Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a meta-analysis. Am J Gastroenterol 96:689–696

    PubMed  CAS  Google Scholar 

  • Vilaro MT, Domenech T, Palacios JM, Mengod G (2002) Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants. Neuropharmacology 42:60–73

    PubMed  CAS  Google Scholar 

  • Von Der Ohe MR, Camilleri M, Kvols LK, Thomforde GM (1993) Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea. New Eng J Med 329:1073–1078

    Google Scholar 

  • Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD (1996) Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 16:2352–2364

    PubMed  CAS  Google Scholar 

  • Wardle KA, Sanger GJ (1993) The guinea pig distal colon-a sensitive preparation for the investigation of 5-HT4 receptor-mediated contractions. Br J Pharmacol 110:1593–1599

    PubMed  CAS  Google Scholar 

  • Wardle KA, Bingham S, Ellis ES, Gaster LM, Rushant B, Smith MI, Sanger GJ (1996) Selective and functional 5-hydroxytryptamine4 receptor antagonism by SB 207266. Br J Pharmacol 118:665–670

    PubMed  CAS  Google Scholar 

  • Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA (1992) Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1Da and 5-HT1Db. Proc Natl Acad Sci USA 89:3630–3634

    PubMed  CAS  Google Scholar 

  • Woolley ML, Marsden CA, Fone KC (2004) 5-ht6 receptors. Current Drug Targets 3:59–79

    PubMed  CAS  Google Scholar 

  • Wouters MM, Farrugia G, Schemann M (2007a) 5-HT receptors on interstitial cells of Cajal, smooth muscle and enteric nerves. Neurogastroenterol Motil 19(Suppl 2):5–12

    PubMed  CAS  Google Scholar 

  • Wouters MM, Gibbons SJ, Roeder JL, Distad M, Ou Y, Strege PR, Szurszewski JH, Farrugia G (2007b) Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors. Gastroenterology 133:897–906

    PubMed  CAS  Google Scholar 

  • Xue L, Camilleri M, Locke GR, Schuurkes JA, Meulemans A, Coulie BJ, Szurszewski JH, Farrugia G (2006) Serotonergic modulation of murine fundic tone. Am J Physiol 291:G1180–G1186

    CAS  Google Scholar 

  • Yeo A, Boyd P, Lumsden S, Saunders T, Handley A, Stubbins M, Knaggs A, Asquith S, Taylor I, Bahari B, Crocker N, Rallan R, Varsani S, Montgomery D, Alpers DH, Dukes GE, Purvis I, Hicks GA (2004) Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut 53:1452–1458

    PubMed  CAS  Google Scholar 

  • Young HM, Furness JB (1995) Ultrastructural examination of the targets of serotonin-immunoreactive descending reflexes to the circular muscle of guinea pig small intestine. J Comp Neurol 356:101–114

    PubMed  CAS  Google Scholar 

  • Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL (2005) Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet 44:279–304

    PubMed  CAS  Google Scholar 

  • Zuberi BF, Quraishy MS, Faisal N, Ahmed S (2005) Idiopathic gastroparesis. J Coll Physicians Surgeons Pakistan 15:566–577

    Google Scholar 

Download references

Acknowledgments

The authors are grateful to Dr. Patrick Humphrey and Dr. Sharath Hegde for their comments on the manuscript during its preparation.

Author information

Authors and Affiliations

  1. Pharmacology and Molecular and Cellular Biology Departments, Theravance, Inc, 901 Gateway Boulevard, South San Francisco, CA, 94080, USA

    D. T. Beattie & J. A. M. Smith

Authors
  1. D. T. Beattie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. A. M. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. T. Beattie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beattie, D.T., Smith, J.A.M. Serotonin pharmacology in the gastrointestinal tract: a review. Naunyn-Schmied Arch Pharmacol 377, 181–203 (2008). https://doi.org/10.1007/s00210-008-0276-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-008-0276-9

Keywords

Search

Navigation