Kinetic interactions of dopamine and dobutamine with human catechol-O-methyltransferase and monoamine oxidase in vitro.
Dopamine and dobutamine are often infused together into acutely ill patients requiring temporary support of cardiac and renal function, but whether these catecholamines affect the metabolic clearance of each other is not established. We determined the kinetics of dopamine and dobutamine as substrates and inhibitors of each other, i.e., apparent V(max), K(m), and K(i), with crude preparations of human blood mononuclear cell catechol-O-methyltransferase (COMT) and platelet monoamine oxidase (MAO) at pH 7.4 and 37 degrees C. Values of V(max) for dopamine and dobutamine as substrates for COMT were 0.45 and 0.59 nmol of 3-O-methyl product formed per milligram of protein per minute, whereas those for K(m) were 0.44 and 0.05 mM, respectively. Dopamine and dobutamine were competitive inhibitors of each other in this reaction. The K(i) for dopamine as an inhibitor of dobutamine methylation was 1.5 mM, whereas that for dobutamine as an inhibitor of dopamine methylation was 0.015 mM. Dopamine but not dobutamine was a substrate for MAO. The V(max) for dihydroxyphenylacetaldehyde formation from dopamine was 0.29 nmol/mg protein/min and the K(m) for dopamine was 0.38 mM. Dobutamine was a noncompetitive inhibitor of dopamine oxidation in this reaction (K(i) congruent with 1.19 mM). The high apparent K(m) and K(i) values derived for dopamine and dobutamine when tested with these two human enzymes in vitro suggest that these catecholamines do not interfere with the metabolism of each other when both are infused together at therapeutic concentrations.
Yan
Maohe
M
Department of Pediatrics, Case Western Reserve University, Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Children's Hospital of the University Hospitals of Cleveland, Cleveland, Ohio 44106-6010, USA.
Webster
Leslie T
LT
Blumer
Jeffrey L
JL
D000328:Adult; D000465:Algorithms; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002394:Catechol O-Methyltransferase / Q000097:blood; D065098:Catechol O-Methyltransferase Inhibitors; D004280:Dobutamine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D008745:Methylation; D008995:Monoamine Oxidase / Q000097:blood*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity
D065098:Catechol O-Methyltransferase Inhibitors; D007202:Indicators and Reagents; D008996:Monoamine Oxidase Inhibitors; D011506:Proteins; D004280:Dobutamine; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine