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.
Mustanoja
S M
SM
Department of Physiology, Institute of Biomedicine, P.O.B. 9, 00014 University of Helsinki, Helsinki, Finland. satu.mustanoja@helsinki.fi
Bäck
N
N
Alila-Johansson
A
A
Laakso
M L
ML
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D020926:Medetomidine / Q000494:pharmacology*; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D015016:Yohimbine; D008550:Melatonin; D020926:Medetomidine