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

Veterans Affairs–Nebraska Western Iowa Health Care System, Omaha 68105; and Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178 Submitted 4 May 2004 ; accepted in final form 2 June 2004 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 ED 50 s 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. intravenous infusion; dose response; interaction Address for correspondence: R. D. Reidelberger, Nebraska Western Iowa Health Care System (151), 4101 Woolworth Ave., Omaha, NE 68105 (E-mail: roger.reidelberger{at}med.va.gov )