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Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats

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Abstract

The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2–0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK1 receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK2 receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK1 receptor activation.

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References

  • Anika MS (1982) Effects of cholecystokinin and caerulein on gastric emptying. Eur J Pharmacol 85:195–199

    CAS  PubMed  Google Scholar 

  • Ballinger AB, Clark ML (1994) L-phenylalanine releases cholecystokinin (CCK) and is associated with reduced food intake in humans: evidence for physiological role of CCK in control of eating. Metabolism 43:735–738

    CAS  PubMed  Google Scholar 

  • Beglinger C (1994) Effect of cholecystokinin on gastric motility in humans. Ann New York Acad Sci 713:219–225

    CAS  Google Scholar 

  • Butcher RL, Collins WE, Fugo NW (1974) Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrus cycle of the rat. Endocrinology 94:1704–1708

    CAS  PubMed  Google Scholar 

  • Chang FY, Lee SD, Yeh GH, Wang PS (1994) Comparison of two orogastric feeding markers for measuring gastrointestinal motor functions in rats. Pharmacology 49:151–158

    CAS  PubMed  Google Scholar 

  • Chen TS, Doong ML, Chang FY, Lee SD, Wang PS (1995) Effects of sex steroid hormones on gastric emptying and gastrointestinal transit in rats. Am J Physiol 268:G171–G176

    CAS  PubMed  Google Scholar 

  • Chen TS, Doong ML, Wang SW, Tsai SC, Lu CC, Shih HC, Chen YH, Chang FY, Lee SD, Wang PS (1997) Gastric emptying and gastrointestinal transit during lactation in rats. Am J Physiol 272:G626–G631

    CAS  PubMed  Google Scholar 

  • Chey WY, Hitanant S, Hendricks J, Lorber SH (1970) Effect of secretin and cholecystokinin on gastric emptying and gastric output in man. Gastroenterology 58:820–827

    CAS  PubMed  Google Scholar 

  • Debas HT, Farooq O, Grossman MI (1975) Inhibition of gastric emptying is a physiological action of cholecystokinin. Gastroenterology 68:1211–1217

    CAS  PubMed  Google Scholar 

  • Doong ML, Lu CC, Kau MM, Tsai SC, Chiao YC, Chen JJ, Yeh JY, Lin H, Huang SW, Chen TS, Chang FY, Wang PS (1998) Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats. Br J Pharmacol 124:1123–1130

    CAS  PubMed  Google Scholar 

  • Fioramonti J, Fargeas MJ, Bertrand V, Pradayrol L, Buéno L (1994) Induction of postprandial intestinal motility and release of cholecystokinin by polyamines in rats. Am J Physiol 267:G960–G965

    CAS  PubMed  Google Scholar 

  • Flanagan LM, Verbalis JG, Stricker EM (1989) Effects of anorexic treatments on gastric motility in rats. Am J Physiol 256:R955–R961

    CAS  PubMed  Google Scholar 

  • Gibbs J, Young RC, Smith GP (1973) Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 84:488–495

    CAS  PubMed  Google Scholar 

  • Gibbs J, Falasco JD, McHugh PR (1976) CCK-decreased food intake in rhesus monkeys. Am J Physiol 230:15–18

    CAS  PubMed  Google Scholar 

  • Goodwin TM, Millar L, North L, Abrams LS, Weglein RC, Holland ML (1995) The pharmacokinetics of the oxytocin antagonist atosiban in pregnant women with preterm uterine contractions. Am J Obstet Gynecol 173:913–917

    CAS  PubMed  Google Scholar 

  • Hadley ME (1996) Neurohypophysial hormones. In: Hadley ME (ed) Endocrinology, 4th edn. Prentice-Hall, Englewood Cliffs, pp 127–149

  • Hashmonai M, Torem S, Argov S, Barzilai A, Schramek A (1979) Prolonged post-vagotomy gastric atony treated by oxytocin. Br J Surg 66:550–551

    CAS  PubMed  Google Scholar 

  • Hill DR, Woodruff GN (1990) Differentiation of central cholecystokinin receptor binding sites using the non-peptide antagonists MK329 and L-365,260. Brain Res 526:276–283

    CAS  PubMed  Google Scholar 

  • Hill DR, Campbell NJ, Shaw TM, Woodruff GN (1987) Autoradiographical localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonist. J Neurosci 10:1070–1081

    Google Scholar 

  • Holzer P (1985) Stimulation and inhibition of gastrointestinal propulsion induced by substance P and substance K in the rat. Br J Pharmacol 86:305–312

    Google Scholar 

  • Hwu CM, Tsai SC, Lau CP, Pu HF, Wang TL, Chiang ST, Wang PS (1992) Increased concentrations of atrial and plasma atrial natriuretic peptide in castrated male rats. Life Sci 52:205–212

    Article  Google Scholar 

  • Innis RB, Synder SH (1980) Distinct cholecystokinin receptors in brain and pancreas. Proc Natl Acad Sci USA 77:6917–6921

    CAS  PubMed  Google Scholar 

  • Jin HO, Lee KY, Chang TM, Chey WY, Dubois A (1994) Physiological role of cholecystokinin on gastric emptying and acid output in dogs. Digest Dis Sci 39:2306–2314

    CAS  PubMed  Google Scholar 

  • Johnson LR (1991) Gastrointestinal physiology, 4th edn. Mosby, St. Louis

  • Kopin AS, Lee YM, McBride EW, Miller LJ, Lu M, Lin HY, Kolakowski LF, Beinborn M (1992) Expression cloning and characterization of the canine parietal cell gastrin receptor. Proc Natl Acad Sci USA 89:3605–3609

    CAS  PubMed  Google Scholar 

  • Lu L, Huang M, Liu Z, Ma L (2000) Cholecystokinin-B receptor antagonists attenuate morphine dependence and withdrawal in rats. Neuroreport 11:829–832

    CAS  PubMed  Google Scholar 

  • Makovec F, Bani M, Chiste R, Revel L, Rovati LC, Setnikar L (1986) Different peripheral and central antagonistic activity of new glutaramic acid derivatives on satiety induced by cholecystokinin in rats. Regul Pept 16:281–290

    CAS  PubMed  Google Scholar 

  • Mangel AW, Koegel A (1984) Effects of peptides on gastric emptying. Am J Physiol 246:G342–G345

    CAS  PubMed  Google Scholar 

  • Margolis RL, Moran TH, McHugh PR (1989) In vitro response of rat gastrointestinal segments to cholecystokinin and bombesin. Peptides 10:157–161

    CAS  PubMed  Google Scholar 

  • McCann MJ, Verbalis JG, Stricker EM (1989) LiCl and CCK inhibit gastric emptying and feeding, and stimulate OT secretion in rats. Am J Physiol 256:R463–R468

    CAS  PubMed  Google Scholar 

  • Melin P, Vilhardt H, Lindeberg G, Larsson LE, Akerlund M (1981) Inhibitory effect of O-alkylated analogues of oxytocin and vasopressin on human and rat myometrial activity. J Endocrinol 88:173–180

    CAS  PubMed  Google Scholar 

  • Miller MS, Galligan JJ, Burks TF (1981) Accurate measurement of intestinal transit in the rat. J Pharmacol Meth 6:211–217

    CAS  PubMed  Google Scholar 

  • Monstein HJ, Nylander AG, Salehi A, Chen D, Lundquist I, Hakanson R (1996) Cholecystokinin-A and cholecystokinin-B/gastrin receptor mRNA expression in the gastrointestinal tract and pancreas of rat and man. A polymerase chain reaction study. Scand J Gastroenterol 31:383–390

    CAS  PubMed  Google Scholar 

  • Moran TH, McHugh PR (1982) Cholecystokinin suppresses food intake by inhibiting gastric emptying. Am J Physiol 242:R491–R497

    CAS  PubMed  Google Scholar 

  • Moran TH, Robinson PH, Goldrich MS, McHugh PR (1986) Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res 362:175–179

    CAS  PubMed  Google Scholar 

  • Moran TH, Smith GP, Hostetler AM, McHugh PR (1987) Transport of cholecystokinin (CCK) binding sites in subdiaphragmatic vagal branches. Brain Res 415:149–152

    CAS  PubMed  Google Scholar 

  • Moran TH, Kornbluh R, Moore K, Schwartz GJ (1994) Cholecystokinin inhibits gastric emptying and contracts the pyloric sphincter in rats by interacting with low affinity CCK receptor sites. Regul Pept 52:165–172

    CAS  PubMed  Google Scholar 

  • Moriarty P, Dimaline R, Thompson DG, Dockray GJ (1997) Characterization of cholecystokinin A and cholecystokinin B receptors expressed by vagal afferent neurons. Neuroscience 79:905–913

    Google Scholar 

  • Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D, Fejgin M, Liston RM, Dansereau J, Mazor M, Shalev E, Boucher M, Glezerman M, Zimmer EZ, Rabinovici J (2000) Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. Am J Obstet Gynecol 182:1191–1199

    CAS  PubMed  Google Scholar 

  • Murphy RB, Smith GP, Gibbs J (1987) Pharmacological examination of cholecystokinin (CCK-8)-induced contractile activity in the rat isolated pylorus. Peptides 8:127–134

    CAS  PubMed  Google Scholar 

  • Petring OU (1989) The effect of oxytocin on basal and pethidine-induced delayed gastric emptying. Br J Clin Pharmacol 28:329–332

    CAS  PubMed  Google Scholar 

  • Pisegna JR, De Weerth A, Huppi K, Wank SA (1992) Molecular cloning of human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. Biochem Biophys Res Commun 189:296–303

    CAS  PubMed  Google Scholar 

  • Raybould HE, Taché Y (1988) Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats. Am J Physiol 255:G242–G246

    CAS  PubMed  Google Scholar 

  • Reidelberger RD, O'Rourke MF (1989) Potent cholecystokinin antagonist L-364,718 stimulates food intake in rats. Am J Physiol 257:R1512–R1518

    CAS  PubMed  Google Scholar 

  • Renaud LP, Tang M, McCann MJ, Stricker EM, Verbalis JG (1987) Cholecystokinin and gastric distension activate oxytocinergic cells in rat hypothalamus. Am J Physiol 253:R661–R665

    CAS  PubMed  Google Scholar 

  • Rodriguez-Membrilla A, Martinez V, Vergara P (1995) Peripheral and central cholecystokinin receptors regulate postprandial intestinal motility in the rat. J Pharmacol Exp Ther 275:486–493

    CAS  PubMed  Google Scholar 

  • Ruckebusch M, Fioramonti J (1975) Electrical spiking activity and propulsion in small intestine in fed and fasted rats. Gastroenterology 68:1500–1508

    PubMed  Google Scholar 

  • Schick RR, Reilly WM, Roddy DR, Yaksh TL, Go VLW (1987) Neuronal cholecystokinin-like immunoreactivity is postprandially released from primate hypothalamus. Brain Res 418:20–26

    CAS  PubMed  Google Scholar 

  • Silvente-Poirot S, Dufresne M, Vaysse N, Fourmy D (1993) The peripheral cholecystokinin receptors. Eur J Biochem 215:513–529

    CAS  PubMed  Google Scholar 

  • Steel RD, Torrie JH (1960) Principles and procedures of statistics. McGraw-Hill, New York

  • Stock S, Uvnas-Moberg K (1987) L-vasopressin inhibits oxytocin-induced increases of plasma levels of insulin in conscious dogs. Acta Physiol Scand 130:55–61

    CAS  PubMed  Google Scholar 

  • Tindal JS (1974) Stimuli that cause the release of oxytocin. In: Handbook of physiology, vol 4. Endocrinology. The pituitary gland and its neuroendocrine control. American Physiological Society, Bethesda, pp 257–267

  • Varga G, Scarpignato C (1996) Camostate- and caerulein-induced delay of gastric emptying in the rat: effect of CCK receptor antagonists. Eur J Pharmacol 306:153–159

    CAS  PubMed  Google Scholar 

  • Verbalis JG, McCann MJ, McHale CM, Stricker EM (1986a) Oxytocin secretion in response to cholecystokinin and food intake: differentiation of nausea from satiety. Science 232:1417–1419

    CAS  PubMed  Google Scholar 

  • Verbalis JG, McHale CM, Gardiner TW, Stricker EM (1986b) Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats. Behav Neurosci 100:466–475

    CAS  PubMed  Google Scholar 

  • Wakerley JB, Lincoln OW (1971) Intermittent release of oxytocin during suckling in the rat. Nature 233:180–181

    Google Scholar 

  • Walsh JH (1987) Gastrointestinal hormones. In: Johnson LR (ed) Physiology of the gastrointestinal tract, vol 1. Raven, New York, pp 195–206

  • Wank SA, Pisegna JR, De Weerth A (1992) Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc Natl Acad Sci USA 89:8691–8695

    CAS  PubMed  Google Scholar 

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Acknowledgements

The present study was supported by a research grant (no. NSC90-2314-B-075-031) from the National Science Council, Taiwan, Republic of China. Devazepide and L-365,260 were kindly provided by ML Laboratories PLC, Liverpool, UK.

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Correspondence to Paulus S. Wang.

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Wu, CL., Hung, CR., Chang, FY. et al. Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats. Naunyn-Schmiedeberg's Arch Pharmacol 367, 406–413 (2003). https://doi.org/10.1007/s00210-003-0690-y

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  • DOI: https://doi.org/10.1007/s00210-003-0690-y

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