MECHANISMS OF MELATONIN INHIBITION OF NEUROHYPOPHYSEAL HORMONE-RELEASE FROM THE RAT HYPOTHALAMUS IN-VITRO

Although melatonin has been reported to influence neurohypophysial hor mone 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 hypothalamu s in vitro was therefore determined, The agents employed were atropine , a muscarinic cholinergic antagonist; mecamylamine, a nicotinic choli nergic antagonist; atenolol, a beta-adrenergic antagonist; phentolamin e, a nonselective alpha-adrenergic antagonist; prazosin, a selective a lpha-adrenergic antagonist; haloperidol, a dopaminergic antagonist; na loxone, an opioid antagonist; and ibuprofen, a cyclooxygenase inhibito r, Rat hypothalami were incubated in either medium alone or medium con taining melatonin or melatonin and antagonist, and hormone release det ermined, Melatonin (43 nM) significantly inhibited (p < 0.05) vasopres sin and oxytocin release. Inhibition was still observed in the presenc e of atenolol, phentolamine, and naloxone, suggesting that neither adr energic 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 at tenuated in the presence of prazosin (10 - 8 and 10 - 6 M), This study suggests that melatonin may influence neurohypophysial hormone releas e through modulation of afferent pathways mediated by acetylcholine, d opamine, and/or prostaglandin. (C) 1998 Elsevier Science Inc.