Juszczak M, Boczek-Leszczyk E
Department of Pathophysiology and Experimental Neuroendocrinology, Medical University of Łódź, Poland.
J Physiol Pharmacol. 2008 Sep;59(3):553-62.
The aim of the present study was to investigate the effect of peptide NK-1 and NK-2 receptors agonists and antagonists (and their natural ligands, i.e., substance P and neurokinin A) on the oxytocin (OT) secretion from the rat neurohypophysis into the blood. Intracerebroventricular (icv) injection of substance P (SP) or highly selective NK-1 receptor agonist--[(Sar(9),Met(O2)(11))-Substance P]-- significantly stimulated the OT secretion from the rat neurohypophysis into the general circulation. After icv injection of the NK-1 receptor antagonist--[(Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11)]--the blood plasma OT concentration was significantly lower, when compared to vehicle-injected animals. On the other hand, the icv administered neurokinin A (NKA) and the NK-2 receptor agonist--[(beta-Ala(8))-Neurokinin A (4-10)]--were essentially inactive in modifying OT secretion. However, such injection of the NK-2 receptor antagonist--[(Tyr(5),D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10)]--was found to diminish the blood plasma hormone concentration, when compared to vehicle-injected animals. The neurohypophysial content of OT was decreased in NKA-treated rats, but neither the NK-2 receptor agonist nor antagonist were able to affect the OT output from the rat posterior pituitary. The hypothalamic levels of OT were not modified by any of the studied peptides. The present data strongly indicate a major role for the tachykinin NK-1 receptor in SP- and/or NKA-dependent regulation of OT secretion from the rat neurohypophysis into the blood.
本研究的目的是探讨肽类NK-1和NK-2受体激动剂及拮抗剂（以及它们的天然配体，即P物质和神经激肽A）对大鼠神经垂体中催产素（OT）分泌入血的影响。脑室内（icv）注射P物质（SP）或高选择性NK-1受体激动剂——[(Sar(9),Met(O2)(11))-P物质]——可显著刺激大鼠神经垂体向体循环分泌OT。icv注射NK-1受体拮抗剂——[(Tyr(6),D-Phe(7),D-His(9))-P物质(6-11)]——后，与注射赋形剂的动物相比，血浆OT浓度显著降低。另一方面，icv给予神经激肽A（NKA）和NK-2受体激动剂——[(β-Ala(8))-神经激肽A(4-10)]——在改变OT分泌方面基本无活性。然而，与注射赋形剂的动物相比，发现注射这种NK-2受体拮抗剂——[(Tyr(5),D-Trp(6,8,9),Lys-NH2(10))-神经激肽A(4-10)]——可降低血浆激素浓度。NKA处理的大鼠神经垂体中OT含量降低，但NK-2受体激动剂和拮抗剂均不能影响大鼠垂体后叶的OT释放量。所研究的任何一种肽均未改变下丘脑OT水平。目前的数据有力地表明速激肽NK-1受体在P物质和/或NKA依赖的大鼠神经垂体OT分泌入血的调节中起主要作用。
