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 re gulation 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 we re 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 atipamez ole. The effects of medetomidine and atipamezole were also additive: the ma ximum response to atipamezole could be significantly increased by medetomid ine. These results suggest that the two drugs stimulate the melatonin synth esis through different mechanisms: medetomidine through alpha(2)-adrenocept ors and atipamezole possibly through nonadrenergic mechanisms. The results differ from previous in vivo experiments suggesting that alpha(2)-adrenocep tor ligands affect melatonin synthesis both centrally and locally in the pi neal gland. The local effects are most likely masked under the central regu latory systems in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.