Differential inhibitory effects of melatonin analogs and three naphthalenic ligands on 2-[125I]iodomelatonin binding to chicken tissues

• Published in: Journal of pineal research 1997-10, Vol.23 (3), p.148-155
• Main Authors: Pang, Celia S., Tang, Pak L, Song, Yong, Pang, Shiu F., Ng, Kai W., Guardiola-Lemaitre, Beatrice, Delagrange, Philippe, Brown, Gregory M.
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Binding, Competitive - drug effects; Biological and medical sciences; Brain - metabolism; Chickens; diurnal rhythms; Female; Fundamental and applied biological sciences. Psychology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; IC50; Kidney - metabolism; Ligands; Lung - metabolism; Male; Melatonin - analogs & derivatives; Melatonin - metabolism; Melatonin - pharmacology; melatonin receptors; Membranes - metabolism; Naphthalenes - pharmacology; naphthalenic ligands; pineal gland; Radioligand Assay; Receptors, Cell Surface - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Melatonin; Spleen - metabolism; Tryptamines - pharmacology; Vertebrates: endocrinology
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.1997.tb00348.x

Pang CS, Tang PL, Song Y, Pang SF, Ng KW, Guardiola‐Lemaitre B, Delagrange P, Brown G.M. Differential inhibitory effects of melatonin analogs and three naphthalenic ligands on 2‐[l25I]iodomelatonin binding to chicken tissues. J. Peneal Res. 1997; 23:148–155. © Munksgaard, Copenhagen We have compared the 50% inhibition values of 2‐[l25I]iodomelatonin ([125I]Mel) competition curves by melatonin and 3 naphthalenic ligands, N‐[2‐(7‐methoxy‐l‐naphthyl) ethyl] cyclobutane carboxamide (S20642), N‐propyl N‐[2‐(7‐methoxy‐l‐naphtyl) ethyl] urea (S20753), and N‐[2‐(7‐methoxy‐l‐naphthyl) ethyl] crotonamide (S20750), using membrane preparations of four tissues (lung, spleen, brain, and kidney) of the chicken simultaneously. In retired breeders, we have demonstrated that the affinities of S20642 were similar in the lung and spleen. However they were 2‐fold lower in the brain and 80‐fold lower in the kidney. Similar differential binding affinities to the melatonin receptors were observed in the four tissues of young male chicks. This suggests that age and sex have little influence on the differential inhibitory properties of melatonin and S20642 in the tissues studied. The addition of guanosine 5'‐0‐thiotriphosphate (GTPyS), which encouraged the uncoupling of melatonin receptor to the G protein complex, lowered the binding affinity of melatonin and S20642 in the tissues studied but their differentia] affinities in the four tissues were however maintained. The affinities of 5‐methoxy‐N‐cyclopropanoyltryptamine (CPMT) in the kidney were also 5–10‐fold lower than those in the lung, spleen, and brain of young male chicks. The distinctive differential affinities of melatonin, S20642, and CPMT for [l25I]Mel binding sites in the chicken lung, spleen, brain, and kidney indicated that the binding sites in these tissues are heterogeneous. Our study implicated that the naphthalenic ligand S20642 may be a useful melatonin analog to distinguish melatonin receptor subtypes in tissues and a possible drug candidate worthwhile for further investigations.