The role of the cAMP/PKA signalling pathway in the inhibitory influence of melatonin on oxytocin and vasopressin secretion from the rat hypothalamo-neurohypophysial system.

Abstract

Melatonin was found to inhibit forskolin-stimulated oxytocin (OT) and vasopressin (VP) release in vitro. The purpose of the present investigation was to evaluate the contribution of the cyclic 3',5'-adenosine monophosphate/protein kinase A (cAMP/PKA) signalling pathway in melatonin-dependent inhibition of OT and VP secretion from the rat hypothalamo-neurohypophysial (H-NH) system in vitro. The H-NH explants were placed in 1 ml of normal Krebs-Ringer (nK-R) buffer and first preincubated for 30 min in control buffer or in the presence of PKA inhibitor, i.e. cAMPS-Rp or H-89. Next, they were incubated in nK-R buffer {fluid F1} and then in buffer as F1 enriched with melatonin (10-9 M or 10-7 M) and/or PKA activator, i.e. cAMP analogue (8-Br-cAMP), or their vehicles {fluid F2}. After 20 min of incubation in fluid F1 and then F2, the media were collected and frozen, to be assayed for OT and VP by the RIA. 8-Br-cAMP increased OT and VP secretion when the H-NH explants were preincubated in control medium, while PKA inhibitors eliminated its stimulatory effect on OT and VP release. Melatonin (10-7 M) diminished basal OT and VP output from the H-NH system, and inhibited (at both concentrations studied) the cAMP analogue-stimulated release of both neurohormones under control conditions. The effect of melatonin on OT and VP release was completely blocked when cAMPS-Rp, but not H-89, was used to disrupt the cAMP/ /PKA pathway. Melatonin employs the cAMP/PKA signalling pathway to inhibit OT and VP secretion from the rat H-NH system; nonethe-less, other cAMP-mediated mechanisms are not excluded.