Inhibitory effect of PYY on vagally stimulated acid secretion is mediated predominantly by Y1 receptors.
Inhibitory effect of PYY on vagally stimulated acid secretion is mediated predominantly by Y1 receptors.
复制标题
PYY 对迷走神经刺激的酸分泌的抑制作用主要由 Y1 受体介导。
作者：
K. C. Lloyd;D. Grandt;K. Aurang;V. Eysselein;M. Schimiczek;J. Reeve
肽YY（PYY）的两种分子形式PYY-（1- 36）和PYY-（3- 36）在兔的肠道和血液中含量丰富。我们以前已经证明PYY-（1- 36）（PYYI）等效力地激活Y1和Y2受体，并且PYY-（3- 36）（PYY II）是Y2受体的高度选择性激动剂。在本研究中，我们研究了外源性输注PYY对慢性胃瘘清醒家兔迷走神经刺激胃酸分泌的影响。为了确定介导这种效应的特异性PYY受体，我们使用了高度选择性的Y1激动剂Pro34-PYY、合成PYY和Y2选择性激动剂PYY II。在开始静脉输注PYY I、PYY II或[Pro 34]-PYY 180分钟后30分钟，静脉推注胰岛素（0.125 U/kg），静脉推注50 μ g/kg阿托品，随后立即皮下注射500 μ g/kg，引起迷走神经酸分泌刺激。在输注200 pmol.kg 1.h-1 PYY I期间，在注射胰岛素后60分钟，酸输出被显著抑制至最大酸输出的45 +/- 13%。同样，输注200 pmol.kg-1.h-1 [Pro 34]-PYY期间的酸排出量被显著抑制至最大值的52 +/- 12%。相比之下，输注200 pmol.kg-1. h-1 PYY II期间的酸排出量未受到显著抑制（最大值的101 +/- 18%）。输注两倍剂量（400 pmol.kg-1. h-1）的PYY II导致酸抑制（51 =最大值的15%），而输注相同剂量的PYY I或[Pro 34]-PYY均未显著增强酸抑制（最大值的28 +/- 11和42 +/- 15%）。这些结果表明，PYY，主要作用于Y1受体，是一个有效的抑制迷走神经刺激的酸分泌成年兔。
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.