Inhibitory effect of PYY on vagally stimulated acid secretion is mediated predominantly by Y1 receptors.
Two molecular forms of peptide YY (PYY), PYY-(1--36) and PYY-(3--36), are abundant in rabbit intestine and blood. We have previously shown that PYY-(1--36) (PYYI) activates equipotently Y1 and Y2 receptors and PYY-(3--36) (PYY II) is a highly selective agonist for Y2 receptors. In the present study, we examined the effect of exogenous infusion of PYY on vagally stimulated gastric acid secretion in awake rabbits with chronic gastric fistula. To determine the specific PYY receptor(s) that mediates this effect, we used a highly selective Y1 agonist, Pro34-PYY, a synthetic PYY, and a Y2-selective agonist, PYY II. Vagal stimulation of acid secretion was elicited by an intravenous bolus injection of insulin (0.125 U/kg) 30 min after beginning a 180-min intravenous infusion of either PYY I, PYY II, or [Pro34]-PYY after a 50 micrograms/kg i.v. bolus of atropine followed immediately by a 500 micrograms/kg sc injection. During infusion of 200 pmol.kg 1.h-1 PYY I, acid output was significantly inhibited to 45 +/- 13% of maximum acid output 60 min after injection of insulin. Similarly, acid output during infusion of 200 pmol.kg-1.h-1 [Pro34]-PYY was significantly inhibited to 52 +/- 12% of maximum. In contrast, acid output during infusion of 200 pmol.kg-1.h-1 of PYY II was not significantly inhibited (101 +/- 18% of maximum). Infusion of double the dose (400 pmol.kg-1.h-1) of PYY II resulted in acid inhibition (51 = 15% of maximum), whereas infusion of the same dose did not significantly enhance acid inhibition by infusion of either PYY I or [Pro34]-PYY (28 +/- 11 and 42 +/- 15% of maximum). These results indicate that PYY, acting predominantly at Y1 receptors, is a potent inhibitor of vagally stimulated acid secretion in adult rabbits.
Lloyd
K C
KC
Research and Medical Services, Department of Veterans Affairs, West Los Angeles Medical Center, USA.
Grandt
D
D
Aurang
K
K
Eysselein
V E
VE
Schimiczek
M
M
Reeve
J R
JR
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D007328:Insulin; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; D019894:Peptide YY; D001285:Atropine