Localization of melatonin receptors Since 1987, the use of [125I]MEL as a ligand with a high specific activity has permitted studies on the localization of MEL receptors (or more exactly binding sites) of the MEL-1 family (MT1, MT2, and Mel1c).The binding sites appear to be widespread in vertebrates. Comparative distribution studies reveal the presence of MEL binding sites in the brain of five vertebrate classes (fish, amphibian, reptiles, birds, and mammals). The most relevant feature is that the distribution of MEL Inhibitors,research,lifescience,medical binding sites in lower vertebrates is much larger

than in mammals, and they are consistently found in areas associated with retinorecipient and integrative structures of the visual system.43 In mammals the situation is more contrasted. Contrary to what, is generally claimed, in mammals, MEL receptors are Inhibitors,research,lifescience,medical also present in a large number of structures. They have been described in more than 110 brain structures, among them the internal granular layer and the external plexiform layer of the olfactory bulb, lateral septum, scptohippocampal nucleus, caudate putamen bed selleck nucleus of the

stria terminalis, SCN, mediobasal hypothalamic nuclei, paraventricular nuclei of the hypothalamus, paraventricular nuclei of the thalamus, intergeniculate leaflet, central and medial amygdaloid nucleus, inferior colliculus, fasciculus retroflexus, substantia nigra, and frontal, orbitofrontal, and parietal cortex.44-46 Inhibitors,research,lifescience,medical However, Inhibitors,research,lifescience,medical a great variability has been noted in the number and location of labeled structures among the species, as well as large differences in receptor den sity between structures and in the same structures between species. Few structures are common, even among species from the same family,44 and very probably this should be correlated either

to the numerous photoperiodic responses, which are different from one species to another, or to the many different, effects described for MEL (see below). Among all these structures, the pituitary PT, which shows the highest density Inhibitors,research,lifescience,medical of MEL receptors and is the only structure found consistently labeled Tryptophan synthase in all mammals so far studied, and the SCN, which contains MEL receptors in many species, are considered as two major sites for MEL action (see below). However, it. should also be pointed out that MEL receptors/binding sites have been identified in numerous peripheral organs. The role of these receptors has not yet been extensively studied, but their presence explains the reported direct action of MEL, for example, on blood vessels47-49 and on cell-mediated and humoral immune function50 on Leydig and luteal cells.51 Its also indicates that the MEL message can be read at different levels of the organism, which should be taken into account when the potential therapeutic properties of MEL or MEL analogues are considered, especially as specific binding sites have been reported in several neoplastic tissues.