Premium
Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations
Author(s) -
Venegas Carmen,
García José A.,
Escames Germaine,
Ortiz Francisco,
López Ana,
Doerrier Carolina,
GarcíaCorzo Laura,
López Luis C.,
Reiter Russel J.,
AcuñaCastroviejo Darío
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00931.x
Subject(s) - melatonin , pinealectomy , pinealocyte , luzindole , cytosol , mitochondrion , medicine , endocrinology , biology , organelle , pineal gland , intracellular , cytoplasm , chemistry , microbiology and biotechnology , biochemistry , melatonin receptor , enzyme
We studied the subcellular levels of melatonin in cerebral cortex and liver of rats under several conditions. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondrion vary over a 24‐hr cycle, although these variations do not exhibit circadian rhythms. The cell membrane has the highest concentration of melatonin followed by mitochondria, nucleus, and cytosol. Pinealectomy significantly increased the content of melatonin in all subcellular compartments, whereas luzindole treatment had little effect on melatonin levels. Administration of 10 mg/kg bw melatonin to sham‐pinealectomized, pinealectomized, or continuous light‐exposed rats increased the content of melatonin in all subcellular compartments. Melatonin in doses ranging from 40 to 200 mg/kg bw increased in a dose‐dependent manner the accumulation of melatonin on cell membrane and cytosol, although the accumulations were 10 times greater in the former than in the latter. Melatonin levels in the nucleus and mitochondria reached saturation with a dose of 40 mg/kg bw; higher doses of injected melatonin did not further cause additional accumulation of melatonin in these organelles. The results suggest some control of extrapineal accumulation or extrapineal production of melatonin and support the existence of regulatory mechanisms in cellular organelles, which prevent the intracellular equilibration of the indolamine. Seemingly, different concentrations of melatonin can be maintained in different subcellular compartments. The data also seem to support a requirement of high doses of melatonin to obtain therapeutic effects. Together, these results add information that assists in explaining the physiology and pharmacology of melatonin.