Skip to main content
Log in

Central Effects of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Gastric Motility and Emptying in Rats

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Pituitary adenylate cyclase activatingpolypeptide (PACAP) is a new member of thesecretinglucagon-vasoactive intestinal peptide (VIP)peptide family. PACAP is widely distributed not only inthe mammalian brain but also in the gastrointestinal tract.Here, we investigated the effects of central andperipheral administrations of PACAP on gastric motilityand gastric emptying in rats. We found that theintracerebroventricular or intracisternal injection of PACAP increasedgastric motility in a dose-dependent manner. Theintracisternal injection of PACAP delayed gastricemptying. These central effects of PACAP on gastricmotility and emptying were blocked by bilateralvagotomy. In contrast, intravenous administration ofPACAP decreased gastric motility and delayed gastricemptying. The peripheral inhibitory effect wasunaffected by bilateral vagotomy, adrenalectomy,phentolamine, and propranolol. We investigated theeffect of PACAP38 on blood glucose levels (BGL) at thesame doses as those used in the gastric motility andemptying studies in urethane-anesthetized rats. Theintravenous but not intracerebroventricular injection ofPACAP38 (1-8 nmol/rat) produced a significant increasein the BGL. We conclude that PACAP has opposite central and peripheral effects on gastricmotility, ie, central PACAP activates the vagal pathwayin the central nervous system to increase gastricmotility, whereas peripheral PACAP inhibits gastricmotility via an unknown pathway. The delay in gastricemptying after the central administration of PACAP mightbe due to the lack of coordinated gastropyloroduodenalcontraction, whereas that after the peripheral administration might be due to the inhibitionof gastric contraction, and this effect may be relatedto the hyperglycemic action of PACAP.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH: Isolation of a novel 38 residuehypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567-574, 1989

    Google Scholar 

  2. Miyata A, Jiang L, Dahl RD, Kitada C, Kubo K, Fujino M, Minamino N, Arimura A: Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun 170:643-648, 1990

    Google Scholar 

  3. Arimura A: Pituitary adenylate cyclase activating polypeptide (PACAP): Discovery and current status of research. Regul Pept 37:287-303, 1992

    Google Scholar 

  4. Christophe J: Type 1 receptors for PACAP (a neuropeptide even more important than VIP? ). Biochem Biophys Acta 1154:183-199, 1993

    Google Scholar 

  5. Arimura A, Somogyvari-Vigh A, Miyata A, Mizuno K, Coy DH, Kitada C: Tissue distribution of PACAP as determined by RIA: Highly abundant in the rat brain and testes. Endocrinology 129:2787-2789, 1991

    Google Scholar 

  6. Sundler F, Ekblad E, Absood A, Hå kanson R, Köves K, Arimura A: Pituitary adenylate cyclase activating peptide: A novel vasoactive intestinal peptide-like neuropeptide in the gut. Neuroscience 46:439-454, 1992

    Google Scholar 

  7. Gottschall PE, Tatsuno I, Miyata A, Arimura A: Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase activating polypeptide. Endocrinology 127:272-277, 1990

    Google Scholar 

  8. Araki N, Takagi K: Relaxant effect of pituitary adenylate cyclase-activating polypeptide on guinea-pig tracheal smooth muscle. Eur J Pharmacol 216:113-117, 1992

    Google Scholar 

  9. Huang M, Shirahase H, Rorstad OP: Comparative study of vascular relaxation and receptor binding by PACAP and VIP. Peptides 14:755-762, 1993

    Google Scholar 

  10. Katsoulis S, Clemens A, Schwörer H, Creutsfeldt W, Schmidt WE: PACAP is a stimulator of neurogenic contraction in guinea pigileum. Am J Physiol 265:G295-G302, 1993

    Google Scholar 

  11. Schwörer H, Katsoulis S, Creutzfeldt W, Schmidt WE: Pituitary adenylate cyclase-activating peptide, a novel VIP-like gut-brain peptide, relaxes the guinea-pig taenia caeci via apamin-sensitive potassium channels. Naunyn-Schmiedebergs Arch Pharmacol 346:511-514, 1992

    Google Scholar 

  12. Mungan Z, Arimura A, Ertan A, Rossowski WJ, Coy DH: Pituitary adenylate cyclase activating polypeptide relaxes rat gastrointestinal smooth muscle. Scand J Gastroenterol 27:375-380, 1992

    Google Scholar 

  13. Schwörer H, Schmidt WE, Katsoulis S, Creutzfeldt W: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on porcine small intestine smooth muscle. Naunyn-Schmiedebergs Arch Pharmacol 303:R103, 1991

    Google Scholar 

  14. Katsoulis S, Schmidt WE, Schwarzhoff R, Folsch UR, Jin JG, Grider JR, Makhlouf GM: Inhibitory transmission in guinia pig stomach mediated by distinct receptors for pituitary adenylate cyclase-activating peptide. J Pharmacol Exp Ther 278:199-204, 1996

    Google Scholar 

  15. Parkman HP, Pagano AP, Ryan JP: PACAP and VIP inhibit pyloric muscle through VIP/PACAP-preferring receptors. Regul Pept 71:185-190, 1997

    Google Scholar 

  16. Mungan Z, Ertan A, Hammer RA, Arimura A: Effect of pituitary adenylate cyclase activating polypeptide on rat pancreatic exocrine secretion. Peptides 12:559-562, 1991

    Google Scholar 

  17. Mungan Z, Ozmen V, Ertan A, Arimura A: Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) inhibits pentagastrin-stimulated gastric acid secretion in conscious rats. Regul Pept 38:199-206, 1992

    Google Scholar 

  18. Mizumoto A, Fujimura M, Ohtawa M, Ueki S, Hayasi N, Itoh Z, Fujino M, Arimura A: Pituitary adenylate cyclase activating polypeptide stimulates gallbladder motility in conscious dogs. Regul Pept 42:39-50, 1992

    Google Scholar 

  19. Ozawa M, Aono M, Mizuta K, Moriga M, Okuma M: Central administration of PACAP stimulates gastric secretion mediated through the vagal pathway in anesthetized rats. Dig Dis Sci 42:2552-2559, 1997

    Google Scholar 

  20. Akarca US, Hammer RA, Arimura A: Sympathoadrenergic system mediated the central inhibitory effect of PACAP-27 on gastric acid secretion in chronic gastric fistula rats. Am J Gastroent 33:1502, 1993

    Google Scholar 

  21. Morley JE, Horowitz M, Morley PMK, Flood JF: Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice. Peptides 13:1133-1135, 1992

    Google Scholar 

  22. Murase T, Kondo K, Otake K, Oiso Y: Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats. Neuroendocrinology 57:1092-1069, 1993

    Google Scholar 

  23. Seki Y, Suzuki Y, Baskaya MK, Saito K, Takayasu M, Shibuya M, Sugita K: Central cardiovascular effects induced by intracisternal PACAP in dogs. Am J Physiol 269:H135-H139, 1995

    Google Scholar 

  24. Krowicki ZK, Arimura A, Nathan NA, Hornby PJ: Hindbrain effects of PACAP on gastric motor function in the rat. Am J Physiol 272:G1221-G1229, 1997

    Google Scholar 

  25. Ebert R: Control of gastric emptying by regulatory peptides. Z Gastroenterol Verh 23:165-170, 1988

    Google Scholar 

  26. Mangel AW, Koegel A: Effects of peptides on gastric emptying. Am J Physiol 246:G342-G345, 1984

    Google Scholar 

  27. Murthy SN, Ganiban G: Effect of the secretin family of peptides on gastric emptying and small intestinal transit in rats. Peptides 9:583-588, 1988

    Google Scholar 

  28. Osuga Y, Mitsuhashi N, Mizuno M: In vivo effect of pituitary adenylate cyclase activating polypeptide 38 (PACAP38) on the secretion of luteinizing hormone (LH) in male rats. Endocrinol Jpn 39:153-156, 1992

    Google Scholar 

  29. Maeda-Hagiwara M, Taché Y: Central nervous system action of TRH to stimulate gastric emptying in rats. Regul Pept 17:199-207, 1987

    Google Scholar 

  30. Raybould HE, Roberts ME, Dockray GJ: Reflex decreases in intragastric pressure in response to cholecystokinin in rats. Am J Physiol 253:G165-G170, 1987

    Google Scholar 

  31. Krowicki Z, Hornby PJ: Opposing gastric motor responses to TRH and Substance P upon their microinjection into the nucleus rapheobscurus of the rat. Am J Physiol 265:G819-G830, 1993

    Google Scholar 

  32. Scarpignato C, Capovilla T, Bertacci G: Action of caerulein on gastric emptying of the conscious rat. Arch Int Pharmacodyn 246:286-294, 1980

    Google Scholar 

  33. Sanchez Pozo A, Alados JC, Sanchez Medina F: Metabolic changes induced by urethane-anesthesia in rats. Gen Pharmacol 19:281-284, 1988

    Google Scholar 

  34. Taché Y, Garrick T, Raybould H: Central nervous system action of peptides to influence gastrointestinal motor function. Gastroenterology 98:517-528, 1990

    Google Scholar 

  35. Legradi G, Shioda S, Arimura A: Pituitary adenylate cyclase-activating polypeptide-like immunore activity in autonomic regulatory are as of the rat medulla oblongata. Neurosci Lett 176:193-196, 1994

    Google Scholar 

  36. Mulder H, Uddman R, Moller K, Elså s T, Ekblad E, Alumets J, Sundler F: Pituitary adenylate cyclase activating polypeptide is expressed in autonomic neurons. Regul Pept 59:121-128, 1995

    Google Scholar 

  37. Palkovits M, Somogyvari-Vigh A, Arimura A: Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain nuclei. Brain Res 699:116-120, 1995

    Google Scholar 

  38. Minami H, McCallum RW: The physiology and pathophysiology of gastric emptying in humans. Gastroente rology 86:1592-1610, 1984

    Google Scholar 

  39. Anvari M, Dent J, Jamieson GG: Mechanics of pusatile transpyloric flow in the pig. J Physiol London 488( 1):193-202, 1995

    Google Scholar 

  40. Dent J, Sun WM, Anvari M: Modulation of the pumping function of gastric body and antropyloric contractions. Dig Dis Sci 39:28S-31S, 1994

    Google Scholar 

  41. Houghton LA, Read NW, Heddle R, Maddern GJ, Downton J, Toouli J, Dent J: Motor activity of the gastric antrum, pylorus, and duodenum under fasted conditions and after a liquid meal. Gastroenterology 94:1276-1284, 1988

    Google Scholar 

  42. Houghton LA, Read NW, Heddle R, Horowitz M, Collins PJ, Chatterton B, Dent J: Re lationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal. Gastroenterology 94:1285-1291, 1988

    Google Scholar 

  43. Tougas G, Anvari M, Dent J, Somers S, Richards D, Stevenson GW: Relation of pyloric motility to pyloric opening and closure in healthy subjects. Gut 33:466-471, 1992

    Google Scholar 

  44. Sekiguchi Y, Kasai K, Hasegawa K, Suzuki Y, Shimoda S: Glycogenolytic activity of pituitary adenylate cyclase activating polypeptide (PACAP) in vivo and in vitro. Life Sci 55:1219-1228, 1994

    Google Scholar 

  45. Hirano T, Niijima A: Effects of 2-deoxy-D-glucose, glucose, and insulin on efferent activity in gastric vagus nerves. Experientia 36:1197-1200, 1980

    Google Scholar 

  46. Fraser R, Horowitz M, Dent J: Hype rglycemia stimulates pyloric motility in normal subjects. Gut 32:475-478, 1991

    Google Scholar 

  47. Hebbard GS, Sun WM, Dent J, Horowitz M: Hype rglycemia affects proximal gastric motor and sensory function in normal subjects. Eur J Gastroenterol Hepatol 8:211-217, 1996

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ozawa, M., Aono, M. & Moriga, M. Central Effects of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Gastric Motility and Emptying in Rats. Dig Dis Sci 44, 735–743 (1999). https://doi.org/10.1023/A:1026661825333

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026661825333

Navigation