Melatonin release from rat pineals in vitro is stimulated by both the alpha(2)-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 (>/=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.