CELLULAR MECHANISMS OF MELATONIN ACTION

The pineal hormone melatonin is involved in photic regulations of vari ous kinds, including adaptation to light intensity, daily changes of l ight and darkness, and seasonal changes of photoperiod lengths. The me latonin effects are mediated by the specific high-affinity receptors l ocalized on plasma membrane and coupled to GTP-binding protein. Two di fferent G proteins coupled to the melatonin receptors have been descri bed, one sensitive to pertussis toxin and the other sensitive to chole ra toxin. On the basis of the molecular structure, three subtypes of t he melatonin receptors have been described: Mel(lA), Mel(1B), and Mel( 1C). The first two subtypes are found in mammals and may be distinguis hed pharmacologically using selective antagonists. Melatonin receptor regulates several second messengers: cAMP, cGMP, diacylglycerol, inosi tol trisphosphate, arachidonic acid, and intracellular Ca2+ concentrat ion ([Ca2+](i)). In many cases, its effect is inhibitory and requires previous activation of the cell by a stimulatory agent. Melatonin inhi bits cAMP accumulation in most of the cells examined, but the indole e ffects on other messengers have been often observed only in one type o f the cells or tissue, until now. Melatonin also regulates the transcr iption factors, namely, phosphorylation of cAMP-responsive element bin ding protein and expression of c-Fos. Molecular mechanisms of the mela tonin effects are not clear but may involve at least two parallel tran sduction pathways, one inhibiting adenylyl cyclase and the other regul ating phospholipide metabolism and [Ca2+](i).