Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions.
The fate and disposition of the melatonin released into the circulation is still poorly understood, and almost all current knowledge is derived from measurements made after a single and often a very large dose of labelled melatonin. In continuous infusion experiments in freely moving rats, we have recently demonstrated that considerable amounts of melatonin must be endogenously released in order to achieve and maintain approximately a 10-fold elevation of the low daytime plasma levels of this hormone. We have now applied this infusion paradigm to study the fate and tissue accumulation of [3H]-melatonin continuously infused under near physiological conditions into the jugular vein for a period of 2 hr. The retention of [3H]-melatonin and chloroform-insoluble [3H]-melatonin-metabolites was measured in almost all body tissues and their subcellular compartments immediately at the end of the infusion period and 6 hr later. At the end of the 2 hr infusion period, about 45% of the administered melatonin was recovered as water-soluble metabolites in the urine and about 20% in the small intestine. Some accumulation of [3H]-melatonin-derived water-soluble radioactivity was also noticed in the liver, colon, adrenals, and pituitary, as well as in the feces. The subcellular distribution of this radioactivity differed between tissues. During the period of 6 hr after the termination of infusion, a considerable amount of melatonin-derived radioactivity was found to become increasingly attached to the proteous interlayer of chloroform extracts of tissues and subcellular fractions, from where it could only be liberated by protease treatment.
Messner
M
M
Psychiatrische Klinik der Universität Göttingen, Germany.
Hardeland
R
R
Rodenbeck
A
A
Huether
G
G
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000378:metabolism; D007262:Infusions, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism*; D014018:Tissue Distribution
D008550:Melatonin