ABSTRACT
I. INTRODUCTION N-Acetyl-5-methoxytryptamine, commonly known as melatonin because of its effects on the epidermal pigment melanin in amphibians and reptiles and its derivation from serotonin, was discovered in bovine tissue slightly over 40 years ago (1,2). Once thought to be exclusively of pineal origin, melatonin is now known to be produced in a variety of other tissues as well, including the retina (3,4), some orbital glands (5,6), gastrointestinal tract (7,8), and possibly in some blood cells (9). Although it is commonplace to make judgments related to melatonin’s actions based on its levels in the serum (which normally range from 5 to 250 pg/mL), relatively little is known concerning the intracellular concentrations of melatonin, although some studies suggest that nuclear levels of melatonin, for example, in brain cells, are considerably higher than concurrent concentrations in the blood (10,11). Additionally, in tissues where melatonin is produced (e.g., in the retina), it is also anticipated that melatonin levels may be much higher than circulating values. It has been proposed that higher intracellular concentrations of melatonin may be possible because of binding proteins that maintain elevated levels against a gradient (12,13).
