title: PYY regulates pancreatic exocrine secretion through multiple receptors in the awake rat.
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, R2 = 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, R2 = 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.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Guarita
authors.forename: X
authors.initials: X
authors.lastname: Deng
authors.forename: Y B
authors.initials: YB
authors.lastname: Huh
authors.forename: P G
authors.initials: PG
authors.lastname: Wood
authors.forename: J R
authors.initials: JR
authors.lastname: Reeve
authors.forename: D C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D010446:Peptide Fragments; D019894:Peptide YY / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D014851:Wakefulness
chemical_list: D010446:Peptide Fragments; D011506:Proteins; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; D019894:Peptide YY