Mechanisms of melatonin inhibition of neurohypophysial hormone release from the rat hypothalamus in vitro.

Although melatonin has been reported to influence neurohypophysial hormone release, no binding has been demonstrated in the neurohypophysial system, suggesting melatonin could affect afferent inputs. The effect of neurotransmitter receptor antagonists on the inhibitory effect of melatonin on neurohypophysial hormone release from the rat hypothalamus in vitro was therefore determined. The agents employed were atropine, a muscarinic cholinergic antagonist; mecamylamine, a nicotinic cholinergic antagonist; atenolol, a beta-adrenergic antagonist; phentolamine, a nonselective alpha-adrenergic antagonist; prazosin, a selective alpha-adrenergic antagonist; haloperidol, a dopaminergic antagonist; naloxone, an opioid antagonist; and ibuprofen, a cyclooxygenase inhibitor. Rat hypothalami were incubated in either medium alone or medium containing melatonin or melatonin and antagonist, and hormone release determined. Melatonin (43 nM) significantly inhibited (p < 0.05) vasopressin and oxytocin release. Inhibition was still observed in the presence of atenolol, phentolamine, and naloxone, suggesting that neither adrenergic nor opioid pathways contribute to the response. The inhibitory effect of melatonin on vasopressin and oxytocin release was abolished (p < 0.05) in the presence of atropine (10[-8] M), mecylamine (10[-6] and 10[-4] M), ibuprofen (10[-4] M) and haloperidol (10[-6] and 10[-5] M). The melatonin-induced inhibition of oxytocin release was also attenuated in the presence of prazosin (10[-8] and 10[-6] M). This study suggests that melatonin may influence neurohypophysial hormone release through modulation of afferent pathways mediated by acetylcholine, dopamine, and/or prostaglandin.