Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone.
OBJECTIVE
The aim of this investigation was to study the variation of catechol-O-methyltransferase (COMT) activity in the human liver, duodenal mucosa and renal cortex, and to investigate the inhibition of COMT by entacapone and tolcapone. This study included 87 samples of human liver, 94 samples of the duodenum and 72 samples of the renal cortex.


RESULTS
The activity of COMT was measured with 3,4-dihydroxybenzoic acid (242 micromol x l(-1)), the methyl acceptor substrate, and adenosyl-L-methionine (44 micromol x l(-1)), the methyl donor substrate. The hepatic activity of COMT activity was significantly higher in men than in women, whereas it was not sex-dependent in the duodenum or renal cortex. The activity of COMT varied 4.4-fold in the liver of men, 2.6-fold in the duodenum and 5.3-fold in the renal cortex. The median estimates of COMT activity were 577, 499, 103 and 159 pmol x min(-1) x mg(-1) in the liver of men and women, in the duodenum and in the renal cortex, respectively.


CONCLUSIONS
Entacapone and tolcapone were powerful inhibitors of COMT and their IC50 estimates were 151 and 773 nM (P = 0.008), respectively, in the liver; consistent results were obtained with the other tissues.
De Santi
C
C
Department of Neurosciences, Medical School, Pisa, Italy.
Giulianotti
P C
PC
Pietrabissa
A
A
Mosca
F
F
Pacifici
G M
GM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001577:Benzophenones / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009596:Nitrophenols; D012737:Sex Factors; D014018:Tissue Distribution; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D009596:Nitrophenols; C071192:entacapone; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase