Melatonin release from rat pineals in vitro is stimulated by both the α2-adrenoceptor agonist medetomidine and the antagonist atipamezole

This study was done to clarify the role of alpha(2)-adrenoceptors in the regulation of pineal melatonin synthesis. Rat pineal glands were incubated in oxygenated Krebs-Ringer solution in perifusion chambers, and perifused for 30 min with alpha(2)-adrenoceptor ligands. The melatonin concentrations were measured from the perifusate by radioimmunoassay. Both medetomidine and atipamezole (greater than or equal to 10(-5) M) increased melatonin release. Yohimbine blocked the increase caused by medetomidine but not by atipamezole. The effects of medetomidine and atipamezole were also additive: the maximum response to atipamezole could be significantly increased by medetomidine. These results suggest that the two drugs stimulate the melatonin synthesis through different mechanisms: medetomidine through alpha(2)-adrenoceptors and atipamezole possibly through nonadrenergic mechanisms. The results differ from previous in vivo experiments suggesting that alpha(2)-adrenoceptor ligands affect melatonin synthesis both centrally and locally in the pineal gland. The local effects are most likely masked under the central regulatory systems in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.