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Physiol. Rev. 78: 687-721, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 3 July 1998, pp. 687-721
Copyright ©1998 The American Physiological Society

Cellular Mechanisms of Melatonin Action

JIRI VANECEK

Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Vanecek, Jiri. Cellular Mechanisms of Melatonin Action. Physiol. Rev. 78: 687-721, 1998. --- The pineal hormone melatonin is involved in photic regulations of various kinds, including adaptation to light intensity, daily changes of light and darkness, and seasonal changes of photoperiod lengths. The melatonin effects are mediated by the specific high-affinity receptors localized on plasma membrane and coupled to GTP-binding protein. Two different G proteins coupled to the melatonin receptors have been described, one sensitive to pertussis toxin and the other sensitive to cholera toxin. On the basis of the molecular structure, three subtypes of the melatonin receptors have been described: Mel1A, Mel1B, and Mel1C. The first two subtypes are found in mammals and may be distinguished pharmacologically using selective antagonists. Melatonin receptor regulates several second messengers: cAMP, cGMP, diacylglycerol, inositol trisphosphate, arachidonic acid, and intracellular Ca2+ concentration ([Ca2+]i). In many cases, its effect is inhibitory and requires previous activation of the cell by a stimulatory agent. Melatonin inhibits cAMP accumulation in most of the cells examined, but the indole effects on other messengers have been often observed only in one type of the cells or tissue, until now. Melatonin also regulates the transcription factors, namely, phosphorylation of cAMP-responsive element binding protein and expression of c-Fos. Molecular mechanisms of the melatonin effects are not clear but may involve at least two parallel transduction pathways, one inhibiting adenylyl cyclase and the other regulating phospholipide metabolism and [Ca2+]i.




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