Effects of two melatonin analogues, S-20098 and S-20928, on melatonin receptors in the pars tuberalis of the rat.
By using quantitative autoradiography, we studied the effects of two drugs related to melatonin on the 2-(125)I-melatonin binding in the pars tuberalis (PT) of rats. The drugs tested were two naphthalenic analogues of melatonin, S-20098 (N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide), an agonist, and S-20928 (N-[2-(1-naphthyl) ethyl] cyclobutyl carboxamide), a putative antagonist. Melatonin (s.c. and i.p.), S-20098 (s.c.), and S-20928 (i.p.) were injected 4 hr before sacrifice. Acute administration of both melatonin and S-20098 decreased melatonin receptor density. In contrast, the putative antagonist S-20928, at a low dose (1 mg/kg), was ineffective on melatonin receptors. It neither affected the 2-(125)I-melatonin specific binding observed in the control group nor did it prevent the decrease in binding induced by melatonin when injected 5 min before the hormone. At a high dose (10 mg/kg), S-20928 totally blocked the effect of melatonin on melatonin receptor density and induced a decrease in binding capacity as melatonin did when injected alone. These results indicate that in the rat pars tuberalis, the melatonin agonist, S-20098, is able to down-regulate melatonin receptors, whereas S-20928 seems to behave as a partial agonist.
Masson-Pévet
M
M
Neurobiologie des Fonctions Rythmiques et Saisonnières, UMR-CNRS 7518, Université Louis Pasteur, Strasbourg, France. mpevet@neurochem.u-strasbg.fr
Recio
J
J
Guerrero
H Y
HY
Mocaer
E
E
Delagrange
P
P
Guardiola-Lemaitre
B
B
Pévet
P
P
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000819:agonists* / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D044094:Receptors, Melatonin
D000081:Acetamides; D009281:Naphthalenes; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C084711:agomelatine; C106874:N-(2-(1-naphthalenyl)ethyl)cyclobutanecarboxamide; C044556:2-iodomelatonin; D008550:Melatonin