Skip to main content
SpringerLink
Log in

PYY Regulates Pancreatic Exocrine Secretion Through Multiple Receptors in the Awake Rat

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

Abstract

Peptide YY (PYY) is one of several regulatory peptides reported to modulate pancreatic secretion. PYY circulates in two forms, PYY1–36 and PYY3–36, and binds to multiple receptor subtypes. We sought to determine if PYY1–36 or PYY3–36 regulates neurally mediated pancreatic secretion through the Y1, Y2, and/or Y5 receptor subtypes. Experiments were conducted in awake, surgically recovered rats. In order to determine the effects of the PYYs on basal pancreatic secretion, either PYY1–36, [Pro34] PYY1–36 (a Y1/Y5 agonist), or PYY3–36 (a Y2/Y5 agonist) were infused for 40 min at doses of 0, 12.5, 25, or 50 pmol/kg/hr while measuring pancreatic juice volume and protein. PYY1–36 increased pancreatic protein secretion at 25 and 50 pmol/kg/hr (P < 0.05) in a dose-dependent manner (P < 0.001, R 2 = 0.990). The Y2/Y5 receptor agonist PYY3–36 significantly inhibited pancreatic juice volume and protein at 12.5 and 25 pmol/kg/hr, but stimulated protein secretion at higher doses (P < 0.001, R 2 = 0.995). The Y1/Y5 agonist, [Pro34] PYY1–36, had no significant effect on basal pancreatic exocrine secretion. Therefore, PYY1–36, PYY3–36 and [Pro34] PYY1–36 produced different, dose-dependent changes on basal pancreatic exocrine secretion. Inhibition of pancreatic secretion by circulating PYY1–36 and PYY3–36 are primarily mediated by the Y2 receptor. Since [Pro34] PYY1–36 did not change pancreatic secretion, it can be concluded that circulating PYY1–36 or PYY3–36 does not modulate pancreatic secretion through the Y1 or Y5 receptors. Since the stimulatory effects of PYY1–36 on pancreatic secretion could not be explained by the actions of PYY3–36 or [Pro34] PYY1–36 on Y1 or Y2 receptors, and since PYY1–36 fails to bind to Y3 or Y4 receptors, we also conclude that PYY1–36 may stimulate pancreatic secretion in a dose-dependent mechanism through a PYY receptor subtype different from Y1, Y2, Y3, Y4 or Y5.

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

  1. Tatemoto K: Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Natl Acad Sci USA 79:2514-2518, 1982

    Google Scholar 

  2. Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, Reeve JR Jr: Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 51:151-159, 1994

    Google Scholar 

  3. Taylor IL: Distribution and release of peptide YY in dog measured by specific radioimmunoassay. Gastroenterology 88:731-737, 1985

    Google Scholar 

  4. Greeley GH Jr, Hill FL, Spannagel A, Thompson JC: Distribution of peptide YY in the gastrointestinal tract of the rat, dog, and monkey. Regul Pep 18:155-163, 1987

    Google Scholar 

  5. Aponte GW, Park K, Hess R, Garcia R, Taylor IL: Mealinduced peptide tyrosine inhibition of pancreatic secretion in the rat. FASEB J 3:1949-1955, 1989

    Google Scholar 

  6. Pappas TN, Debas HT, Taylor IL: Enterogastrone-like effect of peptide YY is vagally mediated in the dog. J Clin Invest 77:49-53, 1986

    Google Scholar 

  7. Pappas TN, Debas HT, Goto Y, Taylor IL: Peptide YY inhibits meal-stimulated pancreatic and gastric secretion. Am J Physiol 248:G118-G123, 1985

    Google Scholar 

  8. Putnam WS, Liddle RA, Williams JA: Inhibitory regulation of rat exocrine pancreas by peptide YY and pancreatic polypeptide. Am J Physiol 256:G698-G703, 1989

    Google Scholar 

  9. Adrian TE, Savage AP, Sagor GR, Allen JM, Bacarese-Hamilton AJ, Tatemoto K, Polak JM, Bloom SR: Effect of peptide YY on gastric, pancreatic, and biliary function in humans. Gastroenterology 89:494-499, 1985

    Google Scholar 

  10. Lluis F, Gomez G, Fujimura M, Greeley GH Jr, Thompson JC: Peptide YY inhibits pancreatic secretion by inhibiting cholicystokinin release in the dog. Gastroenterology 94:137-144, 1988

    Google Scholar 

  11. Holst JJ, Rasmussen TN, Harling H, Schmidt P: Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas. Pancreas 8:80-87, 1993

    Google Scholar 

  12. Nagain C, Chariot J, Roze C: Differential effects of peptide YY, neuropeptide Y, and sigma ligands on neurally stimulated external pancreatic secretion in the rat. Pancreas 10:123-130, 1995

    Google Scholar 

  13. Tohno H, Sarr MG, DiMagno EP: Intraileal carbohydrate regulates canine postprandial pancreaticobiliary secretion and upper gut motility. Gastroenterology 109:1977-1985, 1995

    Google Scholar 

  14. Whitcomb DC, Yin M, Curtis JT, Puccio AM, Reeve JR Jr, Sved AF: Centrally mediated pancreatic secretion is stimulated through the Y1 receptor and inhibited through the Y2 receptor. Gastroenterology 108:A400, 1995

    Google Scholar 

  15. Miyasaka K, Kitani K, Green G: The sequential changes in pancreatic exocrine function after abdominal surgery in the rat. Pancreas 1:347-353, 1986

    Google Scholar 

  16. Petersen H, Grossman M: Pancreatic exocrine secretion in anesthetized and conscious rats. Am J Physiol 233:E530-E536, 1977

    Google Scholar 

  17. Blomqvist AG, Herzog H: Y-receptor subtypes-how many more? Trends Neurosci 20:294-298, 1997

    Google Scholar 

  18. Chen CH, Rogers RC: Central inhibitory action of peptide YY on gastric motility in rats. Am J Physiol 269:R787-R792, 1995

    Google Scholar 

  19. Dumont Y, Fournier A, St Pierre S, Quirion R: Comparative characterization and autoradiographic distribution of neuropeptide Y receptor subtypes in the rat brain. J Neurosci 13:73-86, 1993

    Google Scholar 

  20. Hernandez EJ, Whitcomb DC, Vigna SR, Taylor IL: Saturable binding of circulating peptide YY in the dorsal vagal complex of rats. Am J Physiol 266:G511-G516, 1994

    Google Scholar 

  21. Sheikh S, Roach E, Fuhlendorff J, Williams JA: Localization of Y1 receptors for NPY and PYY on vascular smooth muscle cells in rat pancreas. Am J Physiol 260:G250-G257, 1991

    Google Scholar 

  22. Gerald C, Walker MW, Criscione L, Gustafson EL, Batzl-Hartmann C, Smith KE, Vaysse P, Durkin MM, Laz TM, Linemeyer DL, Schaffhauser AO, Whitebread S, Hofbauer KG, Taber RI, Branchek TA, Weinshank RL: A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382:168-171, 1996

    Google Scholar 

  23. Grandt D, Feth F, Rascher W, Reeve JR Jr, Schlicker E, Schimiczek M, Layer P, Goebell H, Eysselein VE, Michel MC: [Pro34] peptide YY is a Y1-selective agonist at peptide YY/ neuropeptide Y receptors. Eur J Pharmacol 269:127-132, 1994

    Google Scholar 

  24. Jin H, Cai L, Lee K, Chang TM, Li P, Wagner D, Chey WY: A physiological role of peptide YY on exocrine pancreatic secretion in rats. Gastroenterology 105:208-215, 1993

    Google Scholar 

  25. Miyasaka K, Green GM: Effect of partial exclusion of pancreatic juice on rat basal pancreatic secretion. Gastroenterology 86:114-119, 1984

    Google Scholar 

  26. Guan D, Phillips WT, Green GM: Pancreatic secretion stimulated by CCK is not mediated by capsaicin-sensitive vagal afferent pathway in awake rats. Am J Physiol 270:G881-G886, 1996

    Google Scholar 

  27. Eysselein VE, Eberlein GA, Grandt D, Schaeffer M, Zehres B, Behn U, Schaefer D, Goebell H, Douglas H, Lee DL, Shively JE, Meyer HE, Reeve JR Jr: Structural characterization of canine PYY. Peptides 11:111-116, 1990

    Google Scholar 

  28. Whitcomb DC, Curtis JT, Puccio AM, Striker EM, Sved AF: Ligand-receptor binding and physiological evidence for a new PYY receptor subtype in the dorsal vagal complex of the rat. Gastroenterology 104:A862, 1993

    Google Scholar 

  29. Yang H, Li WP, Reeve JR Jr, Rivier J, Taché Y: PYY-Preferring receptors in the dorsal vagal complex and its involvement in PYY stimulation of gastric acid secretion in rats. Br J Pharmacol 123:1549-1554, 1998

    Google Scholar 

  30. Grandt D, Siewert J, Sieburg B, Tai O AL, Schimiczek M, Goebell H, Layer P, Eysselein VE, Reeve JR Jr, Muller MK: Peptide YY inhibits exocrine pancreatic secretion in isolated perfused rat pancreas by Y1 receptors. Pancreas 10:180-186, 1995

    Google Scholar 

  31. Jackerott M, Larsson LI: Immunocytochemical localization of the NPY/PYY Y1 receptor in the developing pancreas. Endocrinology 138:5013-5018, 1997

    Google Scholar 

  32. Issoual D, Berger Z, Laugier R: CCK and PYY do not participate in the delayed inhibition of pancreatic secretion, after stimulation by duodenal oleic acid infusion. Regul Pept 36:45-57, 1991

    Google Scholar 

  33. Guan D, Rivard N, Maouyo D, Gettys TW, Morisset J: Importance of cholecystokinin in peptide-YY release in response to pancreatic juice diversion. Regul Pept 43:169-176, 1993

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, and Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania

    D.R. Guarita, X. Deng, Y.B. Huh, P.G. Wood, J.R. Reeve & D.C. Whitcomb

  2. Department of Medicine, UCLA, Los Angeles, California

    D.R. Guarita, X. Deng, Y.B. Huh, P.G. Wood, J.R. Reeve & D.C. Whitcomb

  3. VA Greater Los Angeles Health Care System, CURE: Digestive Diseases Research Center, Los Angeles, California

    D.R. Guarita, X. Deng, Y.B. Huh, P.G. Wood, J.R. Reeve & D.C. Whitcomb

  4. Pittsburgh Veterans Affairs Medical Center, Pittsburgh, Pennsylvania

    D.R. Guarita, X. Deng, Y.B. Huh, P.G. Wood, J.R. Reeve & D.C. Whitcomb

Authors
  1. D.R. Guarita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y.B. Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P.G. Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J.R. Reeve
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D.C. Whitcomb
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guarita, D., Deng, X., Huh, Y. et al. PYY Regulates Pancreatic Exocrine Secretion Through Multiple Receptors in the Awake Rat. Dig Dis Sci 45, 1696–1702 (2000). https://doi.org/10.1023/A:1005550732146

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005550732146

Search

Navigation