Guarita D R, Deng X, Huh Y B, Wood P G, Reeve J R, Whitcomb D C
Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
Dig Dis Sci. 2000 Sep;45(9):1696-702. doi: 10.1023/a:1005550732146.
Peptide YY (PYY) is one of several regulatory peptides reported to modulate pancreatic secretion. PYY circulates in two forms, PYY1-36 and PYY3-36, and binds to multiple receptor subtypes. We sought to determine if PYY1-36 or PYY3-36 regulates neurally mediated pancreatic secretion through the Y1, Y2, and/or Y5 receptor subtypes. Experiments were conducted in awake, surgically recovered rats. In order to determine the effects of the PYYs on basal pancreatic secretion, either PYY1-36, [Pro34] PYY1-36 (a Y1/Y5 agonist), or PYY3-36 (a Y2/Y5 agonist) were infused for 40 min at doses of 0, 12.5, 25, or 50 pmol/kg/hr while measuring pancreatic juice volume and protein. PYY1-36 increased pancreatic protein secretion at 25 and 50 pmol/kg/hr (P < 0.05) in a dose-dependent manner (P < 0.001, R2 = 0.990). The Y2/Y5 receptor agonist PYY3-36 significantly inhibited pancreatic juice volume and protein at 12.5 and 25 pmol/kg/hr, but stimulated protein secretion at higher doses (P < 0.001, R2 = 0.995). The Y1/Y5 agonist, [Pro34] PYY1-36, had no significant effect on basal pancreatic exocrine secretion. Therefore, PYY1-36, PYY3-36 and [Pro34] PYY1-36 produced different, dose-dependent changes on basal pancreatic exocrine secretion. Inhibition of pancreatic secretion by circulating PYY1-36 and PYY3-36 are primarily mediated by the Y2 receptor. Since [Pro34] PYY1-36 did not change pancreatic secretion, it can be concluded that circulating PYY1-36 or PYY3-36 does not modulate pancreatic secretion through the Y1 or Y5 receptors. Since the stimulatory effects of PYY1-36 on pancreatic secretion could not be explained by the actions of PYY3-36 or [Pro34] PYY1-36 on Y1 or Y2 receptors, and since PYY1-36 fails to bind to Y3 or Y4 receptors, we also conclude that PYY1-36 may stimulate pancreatic secretion in a dose-dependent mechanism through a PYY receptor subtype different from Y1, Y2, Y3, Y4 or Y5.
肽YY（PYY）是据报道可调节胰腺分泌的几种调节肽之一。PYY以两种形式循环，即PYY1 - 36和PYY3 - 36，并与多种受体亚型结合。我们试图确定PYY1 - 36或PYY3 - 36是否通过Y1、Y2和/或Y5受体亚型调节神经介导的胰腺分泌。实验在清醒、手术后恢复的大鼠中进行。为了确定PYY对基础胰腺分泌的影响，在测量胰液体积和蛋白质的同时，以0、12.5、25或50 pmol/kg/小时的剂量注入PYY1 - 36、[Pro34]PYY1 - 36（一种Y1/Y5激动剂）或PYY3 - 36（一种Y2/Y5激动剂）40分钟。PYY1 - 36在25和50 pmol/kg/小时时以剂量依赖性方式增加胰腺蛋白质分泌（P < 0.05）（P < 0.001，R2 = 0.990）。Y2/Y5受体激动剂PYY3 - 36在12.5和25 pmol/kg/小时时显著抑制胰液体积和蛋白质，但在更高剂量时刺激蛋白质分泌（P < 0.001，R2 = 0.995）。Y1/Y5激动剂[Pro34]PYY1 - 36对基础胰腺外分泌没有显著影响。因此，PYY1 - 36、PYY3 - 36和[Pro34]PYY1 - 36对基础胰腺外分泌产生了不同的剂量依赖性变化。循环中的PYY1 - 36和PYY3 - 36对胰腺分泌的抑制主要由Y2受体介导。由于[Pro34]PYY1 - 36没有改变胰腺分泌，可以得出结论，循环中的PYY1 - 36或PYY3 - 36不会通过Y1或Y5受体调节胰腺分泌。由于PYY1 - 36对胰腺分泌的刺激作用不能由PYY3 - 36或[Pro34]PYY1 - 36对Y1或Y2受体的作用来解释，并且由于PYY1 - 36不能与Y3或Y4受体结合，我们还得出结论，PYY1 - 36可能通过不同于Y1、Y2、Y3、Y4或Y5的PYY受体亚型以剂量依赖性机制刺激胰腺分泌。
