INHIBITORY EFFECT OF PYY ON VAGALLY STIMULATED ACID-SECRETION IS MEDIATED PREDOMINANTLY BY Y-1 RECEPTORS

Two molecular forms of peptide YY (PW), PYY-(1-36) and PYY-(3-36), are abundant in rabbit intestine and blood. We have previously shown that PYY-(1-36) (PW I) activates equipotently Y-1 and Y-2 receptors and PY Y-(3-36) (PYY II) is a highly selective agonist for Y-2 receptors. In the present study, we examined the effect of exogenous infusion of PYY on vagally stimulated gastric acid secretion in awake rabbits with ch ronic gastric fistula. To determine the specific PW receptor(s) that m ediates this effect, we used a highly selective Y-1 agonist, Pro(34)-P YY, a synthetic PYY, and a Y-2-selective agonist, PYY II. Vagal stimul ation 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 PW I, PYY II, or [Pro(34)]-PYY after a 50 mu g/kg i v bolus of atropine followed immediately by a 500 mu g/kg sc injection . During infusion of 200 pmol . kg(-1). h(-1) PW I, acid output was si gnificantly inhibited to 45 +/- 13% of maximum acid output 60 min afte r injection of insulin. Similarly, acid output during infusion of 200 pmol . kg(-1). h(-1) [Pro(34)]-PYY was significantly inhibited to 52 /- 12% of maximum. In contrast, acid output during infusion of 200 pmo l . kg(-1). h(-1) of PW 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 inhibiti on by infusion of either PW I or [Pro(34)]-PYY (28 +/- 11 and 42 +/- 1 5% of maximum). These results indicate that PYY, acting predominantly at Y-1 receptors, is a potent inhibitor of vagally stimulated acid sec retion in adult rabbits.