Abstract
Melatonin is not only synthesized in the pineal gland and the retina,
but also in numerous other tissues. Extrapineal melatonin is formed
in amounts exceeding by orders of magnitude that found in the pineal
gland. This is particularly valid for the gastrointestinal tract, in
which
several physiological functions such as duodenal bicarbonate secretion
have been elucidated. Melatonin is produced upon neuronal stimuli in
enteroendocrine cells. Duodenal signaling involves the melatonin
receptor MT2 present in enterocytes and in Paneth cells, in the latter
case
causing uroguanylin/guanylin release that leads to enterocytic
activation of the receptor guanylyl cyclase GUCY2C. High amounts of
melatonin
are also found in the bile fluid, with contributions of melatonin
synthesized in cholangiocytes and, presumably, enterohepatic
circulation.
Melatonin is also formed and metabolized in the skin, in which it
contributes to photoprotection. In the cerebellum, melatonin formation
is
upregulated by bacterial lipopolysaccharide and conveys local
anti-inflammatory protection. Increasing evidence indicates that
melatonin does
not easily cross membranes because of lipophilicity, but that
transporters are required.
Melatonin — More than Just a Pineal Hormone by Rüdiger Hardeland in BJSTR
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