Intracellular action mechanisms of the melatonin neuromodulator. Actual state and perspectives

Journal/Book: Salud Ment. 1996; 19: Calz Mexico-Xochimilco #101, Mexico City 22 DF, Mexico. Inst Mex Psiquiatria. 58-61.

Abstract: Melatonin is a hormone secreted by the pineal gland according to the light-dark cycle. Despite that its pharmacological and physiological effects are well known, its mechanism of action still remains to be elucidated. In this article we review the evidence about melatonin interactions with calmodulin. The kinetics of melatonin-calmodulin binding suggest that the hormone modulates cell activity through intracellular binding to the protein at physiological concentration ranges. The melatonin antagonism to calmodulin may allow the hormone to rhythmically modulate many cellular functions. Melatonin tubulin polymerization studies, and cytoskeletal changes in MDCK and N1E-115 cells cultured with melatonin, suggest that at low concentration (10(-9) M), cytoskeletal melatonin effects are mediated by its antagonism to Ca2+- calmodulin. At higher concentrations (10(-5) M), non-specify ice binding of melatonin to tubulin occurs, thus overcoming the melatonin antagonism to Ca2+- calmodulin. Since melatonin and calmodulin are chemical structures phylogenetically well preserved, calmodulin-melatonin interaction probably represents a primary mechanism for bath regulation and synchronization of cell physiology.

Note: Article BenitezKing G, Inst Mexicano Psiquiatria, Div Invest Clin, Dept Neurofarmacol, Calz Mexico Xochimilco 101, Mexico City 14370, DF, MEXICO

Keyword(s): CENTRAL-NERVOUS-SYSTEM; H-3 MELATONIN; N1E-115 CELLS; CALMODULIN; BRAIN; MDCK; PHOSPHODIESTERASE; ORGANIZATION; INHIBITION; INVITRO

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