Chen X, Westfall T C
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104.
J Cardiovasc Pharmacol. 1993 May;21(5):720-4. doi: 10.1097/00005344-199305000-00005.
The effect of intrathecal administration of neuropeptide Y (NPY), NPY COOH-terminal fragments as well as an NPY Y1 receptor ligand on arterial blood pressure (ABP) of anesthetized rat was studied. NPY and all NPY COOH-terminal fragments tested (NPY11-36, NPY14-36 and NPY18-36), believed to act through Y2 receptors produced a dose-related depressor effect (with slight differences in potency) after intrathecal administration. However, intrathecal injection of a reputed NPY Y1 ligand [Leu31,Pro34]-NPY, did not alter arterial pressure significantly. The results suggest that intrathecal NPY produces its depressor effect through activation of Y2 receptors. To test whether these NPY fragments behaved as antagonists or partial agonists, we examined effect of coadministration of NPY and NPY fragments on the depressor effect of NPY. Coadministration of an equimolar dose (0.1 nmol) of NPY and NPY14-36 or NPY18-36 did not change the depressor effect of intrathecal NPY. When a 10-times higher dose (1 nmol) of the NPY fragments was used, the depressor effect of NPY was still not altered, suggesting that the fragments tested did not possess antagonistic effects. We conclude that the depressor effect of intrathecal NPY is mediated primarily by an NPY Y2 receptor subtype.
研究了鞘内注射神经肽Y（NPY）、NPY羧基末端片段以及一种NPY Y1受体配体对麻醉大鼠动脉血压（ABP）的影响。NPY以及所有测试的NPY羧基末端片段（NPY11 - 36、NPY14 - 36和NPY18 - 36），据信通过Y2受体起作用，鞘内注射后产生剂量相关的降压作用（效力略有差异）。然而，鞘内注射一种著名的NPY Y1配体[Leu31，Pro34]-NPY，并未显著改变动脉血压。结果表明，鞘内注射的NPY通过激活Y2受体产生其降压作用。为了测试这些NPY片段是作为拮抗剂还是部分激动剂，我们研究了NPY与NPY片段共同给药对NPY降压作用的影响。等摩尔剂量（0.1 nmol）的NPY与NPY14 - 36或NPY18 - 36共同给药并未改变鞘内注射NPY的降压作用。当使用高10倍剂量（1 nmol）的NPY片段时，NPY的降压作用仍然未改变，这表明所测试的片段不具有拮抗作用。我们得出结论，鞘内注射NPY的降压作用主要由NPY Y2受体亚型介导。
