Oxytocin release from the rat neurohypophysis into the blood: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists

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 - [(Sar9,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 - [(Tyr6,D-Phe7,D-His9)-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 - [(ß-Ala8)-Neurokinin A (4-10)] - were essentially inactive in modifying OT secretion. However, such injection of the NK-2 receptor antagonist - [(Tyr5,D-Trp6,8,9,Lys-NH210)-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.