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

• Published in: Journal of pineal research 1998-10, Vol.25 (3), p.172-176
• Main Authors: Masson-Pévet, M., Recio, J., Guerrero, H. Y., Mocaer, E., Delagrange, Ph, Guardiola-Lemaitre, B., Pévet, P.
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Animals; Autoradiography; Biological and medical sciences; Cell receptors; Cell structures and functions; down-regulation; Down-Regulation - drug effects; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Male; Melatonin - agonists; Melatonin - analogs & derivatives; Melatonin - antagonists & inhibitors; Melatonin - metabolism; melatonin agonist; melatonin antagonist; melatonin receptor; Molecular and cellular biology; Naphthalenes - pharmacology; pars tuberalis; Pineal Gland - drug effects; Pineal Gland - metabolism; rat; Rats; Rats, Wistar; Receptors, Cell Surface - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Melatonin
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.1998.tb00556.x

: 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.