7-ethoxycoumarin deethylation activity in perfused isolated rat brain.
7-ethoxycoumarin (7-EC) deethylation activity was measured in the perfused rat brain in situ. Infusion of 7-EC into a brain through an internal carotid artery resulted in the formation of 7-hydroxycoumarin (7-HC) and its conjugates in the effluent perfusate collected from the superior vena cava. The rate of formation of products was 200 nmol/h/g when 130 microM 7-EC was infused. This value was much higher (more than 100 times) than that determined from the brain microsomal activity ( approximately 1 nmol/h/g), indicating that the activity determined with microsomes was an underestimate. This value was comparable to the activity in the perfused liver (30-50%), suggesting that drug metabolizing enzymes can play important roles within the brain. Pretreatment of rats with P-450 inducers such as phenobarbital and beta-naphthoflavone increased the deethylation activity in the perfused brain, as in the perfused liver. We conclude that the perfused brain is suitable for evaluating drug metabolizing activities under physiological conditions.
Biophysics Division, Research Institute for Electronic Science, Hokkaido University, Sapporo, 060-0812, Japan.
Y
Y
Chikaoka
M
M
Tamura
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003374:Coumarins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology
D003374:Coumarins; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C017299:7-ethoxycoumarin; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital