Melatonin is a highly lipophilic molecule that is capable of diffusing through both cell and nuclear membranes to enter intracellular compartments. Recently, two distinct MLT receptors were identified—a cell membrane, G-protein linked receptor, and a nuclear MLT receptor. The membrane-bound MLT receptor was first characterized by Reppert et al. (29), and is termed the MeL (mti) receptor. The mti receptor binds MLT with a Kd of approximately 0.06 nM, and affects cellular activity by transmitting its signal through second messenger G-proteins (30). A second MLT receptor, termed the Meln (MT2) receptor, has also been described. The MT2 receptor binds MLT with an affinity similar to that of mti. The MT2 receptor is also a membrane-associated, G-protein linked receptor with 60% homology to the mti receptor at the amino acid level
Becker-Andre et al. (32) recently reported that MLT is able to specifically bind to the retinoid Z receptor (RZR) and sub-types and the retinoid orphan receptor (ROR ). However, these receptors have a 100-1000 fold lower binding affinity for MLT than the mt1 receptor. The RZR/ROR receptors belong to the steroid/thyroid hormone receptor superfamily, and show sequence homology to the retinoic acid receptors, RAR and RXR (32,33). The RZR/RORs appear to bind DNA as monomers or homodimers, unlike most members of the steroid hormone receptor superfamily which bind target DNA sequences as heterodimers and homodimers (33). Our laboratory (34), as well as other research groups (31), has subsequently been unable to confirm the binding studies performed by Becker-Andre et al. (32), thus, it is generally believed that the mt1 receptor is the functional MLT receptor.
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Salvation For The Sleep Deprived The Ultimate Guide To Sleeping, Napping, Resting And Restoring Your Energy. Of the many things that we do just instinctively and do not give much of a thought to, sleep is probably the most prominent one. Most of us sleep only because we have to. We sleep because we cannot stay awake all 24 hours in the day.