Characteristic glucuronidation pattern of physiologic concentration of morphine in rat brain.
Formation of conjugated metabolites from morphine at a very low level in brain was studied in vitro in rats. Incubation of a low concentration of 3H-morphine with brain homogenate followed by two successive high-performance liquid chromatographic analyses showed that endogenous morphine is converted by brain enzymes to its 3- and 6-glucuronides (M-3-G and M-6-G), and codeine glucuronide (Cod-G). However, the formation of morphine-6-sulfate was likely to be low if it was produced at all. All of the cerebral hemisphere, brain stem and cerebellum were capable of producing M-3-G, M-6-G and Cod-G, although there were differences in selectivity. The capacity of the brain for glucuronide formation was far less than that of the liver, but UDP-glucuronosyltransferase in brain was much more selective in forming M-6-G and Cod-G than liver enzymes.
Nagano
E
E
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamada
H
H
Oguri
K
K
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003061:Codeine / Q000031:analogs & derivatives / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009020:Morphine / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013687:Telencephalon / Q000378:metabolism
D020719:Glucuronides; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C061773:codeine-6-glucuronide; D014453:Glucuronosyltransferase; C018108:morphine-3-glucuronide; D003061:Codeine