Melatonin (N-acetyl-5-methoxytryptamine) is a product of tryptophan metabolism. It is synthesized in the pineal gland and is secreted to control the circadian rhythm^1-3. Melatonin is also synthesized in the gastrointestinal tract, retina, skin and other tissues where it acts in a autocrine or paracrine manner. The role of melatonin in these tissues is independent of its role in the circadian rhythm, where it plays a role in energy metabolism, physiological growth, differentiation and responsiveness in stress stimuli¹. The pleiotropic effects of melatonin have given rise to various therapeutic possibilities for this molecule. For example; anti-stress, sexual dysfunction, obesity, gallbladder stones^1,4. To date, the only therapeutic uses for melatonin remain to treat sleep disorders, depression, migraine and headaches¹.

Melatonin exerts its effects through two G-protein coupled receptors (GPCRs); melatonin receptor type 1 and melatonin receptor type 2 (MT₁ and MT₂). Like all GPCRs, they have seven transmembrane domains and extracellular N-terminal and cytoplasmic C-terminal tails. The binding of melatonin to either receptor activates G_i, thereby activating PLC, thus increasing intracellular Ca²⁺ levels. Both receptors structurally bind melatonin in the same manner, although MT₂ displays a much higher affinity for the hormone. Just like melatonin levels are detected in many tissues, the expression patterns of the two receptors are also quite broad. For example, MT₁ is detected in the brain, retina and kidneys and MT₂ is expressed in brain and in the retina¹.

MT₁ is involved in sleep regulation and might also have effects on peripheral vasoconstriction. MT₂ may play an important physiological role in the retina and might regulate body temperature¹.