By Ronald Ross Watson
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Additional resources for Melatonin in the Promotion of Health, 2nd Edition
Campbelli, which lack active MT2 receptors . Depending on the tissue and species, MEL can activate different second messenger cascades acting on the same receptor subtype. By using recombinant MEL receptors, it has been shown that the predominant cellular effect of the MEL is the inhibition of forskolin-stimulated cAMP accumulation in the SCN and PT . This effect of MEL is pertussis toxin sensitive, indicating coupling of the receptor to a Gi protein . However, a cholera toxin (inhibitor of Gsα subunit)– sensitive component also mediates the inhibition of forskolin-stimulated cAMP accumulation , implying coupling through a G0 protein.
Although most of the studies in order to provide experimental evidence for the roles of MEL in human have used pharmacological doses of MEL (1 μM and above), a few studies confirmed these functions clinically or perfect experimentally as opposed to physiological doses (below the nanomolar range) of MEL [201,288]. Since several recent publications including ours  have reviewed the current status on multiple physiological functions including the autocrine–paracrine role of MEL, the current treatise emphasizes only a few of them, which proved important in the context of human health.
During the day, AA-NAT activity is lower than HIOMT activity and would be the limiting factor for the synthesis of MEL. The increase in AA-NAT activity at the beginning of the night thus induces the increase in MEL synthesis. During the night, however, HIOMT activity is lower than AA-NAT activity and would thus become the limiting enzyme for MEL production. Consequently, any variation in nighttime HIOMT activity should modulate the rate of MEL synthesis (the amplitude of the nocturnal MEL peak) .