Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Abstract

We compared the effects of the two molecular forms of the brain-gut peptide YY (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received 20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol·kg−1·min−1) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol·kg−1·min−1), either alone or combined, and gastric emptying of saline was measured during the last 10 min of infusion. For comparison, human PYY(3-36) was administered at 0, 17, and 50 pmol·kg−1·min−1. Gastric emptying was decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol·kg−1·min−1 of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50, 100, and 170 pmol·kg−1·min−1 of rat PYY(3-36); and by 35 and 53% in response to 17 and 50 pmol·kg−1·min−1 of human PYY(3-36), respectively. Estimated ED50s were 470 and 37 pmol·kg−1·min−1 for rat PYY(1-36) and PYY(3-36), respectively. In general, within an experiment, coadministration of PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was comparable to that produced when either peptide was given alone. We conclude that 1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36) do not appear to interact in an additive or synergistic manner to inhibit gastric emptying.