Effects of two melatonin analogues, S-20098 and S-20928, on melatonin receptors in the pars tuberalis of the rat

Abstract: By using quantitative autoradiography, we studied the effects of two drugs related to melatonin on the 2- ¹²⁵I-melatonin binding in the pars tuberalis (PT) of rats. The drugs tested were two naphthalenic analogues of melatonin, S-20098 ( N -[2-(7-methoxy-l-naphthyl) ethyl] acetamide), an agonist, and S-20928 ( N -[2-(l-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- ¹²⁵I-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.