Gut melatonin: A potent candidate in the diversified journey of melatonin research

Abstract

After being discovered from the bovine pineal gland by Aaron Lerner and co-workers in the year 1958, various distinguished researchers have reported melatonin (5-methoxy-N-acetyl-tryptamine) from several extra-pineal sources, including the gastrointestinal tract (GIT). In the year 1974, Raikhlin and Kvetnoy first detected this molecule in the gastrointestinal tissue. Later, within the last 45 years, many renowned investigators found that the GIT is a rich source of melatonin, in addition to the pineal gland. In the carp gut, the estimation of Arylalkylamine-N-acetyltransferase (AANAT) mRNA/protein levels, which is the rate-determining enzyme for melatonin biosynthesis in the pineal gland, confirmed the endogenous synthesis of melatonin. The remarkable feature of the pineal gland melatonin is its rhythmic synthesis with a peak at dark-phase and lowest at light-phase in synchronization with seasonal environmental light–dark (LD) cycle. Recent studies on carp demonstrated that the melatonin concentrations and the AANAT protein intensities in different gut segments underwent significant daily fluctuations. However, compared to the melatonin rhythm in the pineal gland, the melatonin profiles in gut tissue displayed daily rhythm in parallel with the feeding cycle of the carp, irrespective of LD conditions of the environment. Notably, in carp, the temporal pattern of the gut melatoninergic system found to vary with the environmental non-photic signal(s), such as food entrainment factors (viz. availability of food, timing of food supply, number(s) of feed per day, quality of food) those act as the most dependable synchronizer(s) in daily rhythm characteristics of gut melatonin and AANAT. Thereby in this review, it appears meaningful to highlight the existing data on the mode of synthesis of melatonin in cells of the digestive tract, and most importantly, the regulation of its synthesis. Finally, in comparison with the dynamic actions of melatonin derived from the pineal gland, this review will lead to underline the role of gut-derived melatonin in a variety of physiological functions.