Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of gonadotrophin-releasing hormone (GnRH), its analogues and melatonin.

The influence of gonadotrophin-releasing hormone (GnRH) and its analogues (i.e., agonist and antagonist) on vasopressin (VP) release from the rat hypothalamo-neurohypophysial (H-N) system was studied both in vitro and in vivo. Additionally, it was determined whether the possible response of vasopressinergic neurones to these peptides could be modified by melatonin through a cAMP-dependent mechanism. In this study we demonstrate, for the first time, that the highly selective GnRH agonist (i.e., [Des-Gly(10),D-His(Bzl)(6),Pro-NHEt(9)]-LHRH; histrelin) stimulates the release of VP from the rat H-N system, while native GnRH and its antagonist remain inactive in modifying this process in vitro. Melatonin significantly inhibited basal and histrelin-induced release of VP in vitro, but displayed no significant influence on VP secretion when GnRH or its antagonist were present in a medium. Melatonin fully suppressed forskolin-stimulated VP release from the rat H-N system. On the other hand, addition of forskolin to a medium containing both histrelin and melatonin did not further alter the inhibitory influence of melatonin on the histrelin-dependent release of VP in vitro. After intracerebroventricular (i.c.v.) infusion of native GnRH or its agonist, blood plasma VP concentration was significantly higher than in control animals, which was accompanied by decreased content of the hormone in the neurohypophysis. Intravenous (i.v.) injection of melatonin did not change, in any subgroup, blood plasma VP concentration, when compared to the vehicle-injected rats. However, the neurohypophysial levels of the hormone were significantly higher after melatonin injection in control, GnRH- and histrelin-infused animals. Our present results suggest that activation of the GnRH receptor in the hypothalamus is involved in stimulation of VP secretion from the rat H-N system. We have also shown that melatonin, at a concentration close to its physiological level in the blood, significantly reduces the in vitro response of vasopressinergic neurones to a GnRH agonist - histrelin; this effect of melatonin could be mediated through intracellular processes that involve, among others, the cAMP-dependent mechanism.

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--[(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.

Effect of melatonin on the vasopressin secretion as influenced by tachykinin NK-1 receptor agonist and antagonist: in vivo and in vitro studies.

The aim of the present study was to investigate the influence of melatonin on vasopressin (AVP) release from the rat hypothalamo-neurohypophysial (H-NH) system, both in vivo and in vitro, possibly modified by the peptide NK-1 and/or NK-2 receptor agonists and antagonists. Highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, has been shown to enhance the AVP release from isolated rat H-NH system in vitro, while the NK-1 receptor antagonist--(Tyr(6),DPhe(7),D-His(9))-Substance P (6-11) as well as the NK-2 receptor selective agonist--(beta-Ala(8))-Neurokinin A (4-10) and antagonist--(Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying AVP secretion. Melatonin inhibited basal release of AVP but was not able to reduce significantly the in vitro response of vasopressinergic neurones to NK-1 receptor agonist. After intracerebroventricular (icv) administration, substance P (SP), neurokinin A (NKA) and the NK-1 receptor agonist (all at the concentration of 10(-7) M/L) significantly enhanced plasma AVP concentration. Such stimulatory effect of the latter peptide on AVP output from the eurohypophysis was reduced by an intravenous (iv) injection of melatonin, which itself (at a concentration of 5 ng/ml) caused a significant decrease in AVP release 10 min after injection. The inhibitory influence of melatonin on the AVP secretion was absent in rats injected icv with both tachykinin receptors antagonists, the NK-2 receptor agonist or NKA. The present data indicate a distinct role for NK-1 receptor in NKA/SP-mediated regulation of AVP release from the rat H-NH system. They have also shown that, under present experimental conditions, the stimulatory effect of NK-1 receptor activation on AVP secretion into the blood is sensitive to inhibitory influence of melatonin.