Pineal melatonin in rats: suppression by the selective alpha2-adrenoceptor agonist medetomidine.
This study was done to clarify the role of alpha2-adrenoceptors in the regulation of pineal melatonin synthesis. A selective alpha2-adrenoceptor agonist, medetomidine, and antagonist, atipamezole, were injected subcutaneously into rats and their pineal melatonin contents were measured by radioimmunoassay. Medetomidine (120 microg/kg) suppressed melatonin at night to a similar extent during the rising and descending phase of melatonin synthesis, but it did not affect the daytime level. A dose of 12 microg/kg was ineffective; doses of 30-180 microg/kg suppressed nocturnal melatonin levels close to the daytime levels. Significant suppression was reached within 15 min and the effect started to fade 3 h after the injection (120 microg/kg). At midday, medetomidine did not inhibit isoproterenol-stimulated synthesis of melatonin. Atipamezole (0.4 or 1.2 mg/kg) had no effect alone, but it counteracted the medetomidine-induced suppression. The effects of alpha2-adrenoceptor ligands on melatonin synthesis depend on the time of day and/or on the activity of the pineal sympathetic nerves.
Mustanoja
S M
SM
Department of Physiology, Institute of Biomedicine, University of Helsinki, Finland.
Hätönen
T
T
Johansson-Alila
A
A
Laakso
M L
ML
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D020926:Medetomidine; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D008550:Melatonin; D007545:Isoproterenol; D020926:Medetomidine