Impairment of the extraneuronal O-methylating system of isoproterenol by stop-flow ischemia in the perfused rat heart.
Effects of ischemia on the extraneuronal O-methylating system were investigated in the perfused rat heart. Ischemia was produced by stopping of the perfusion for 30 min. Isoproterenol (ISO) was used as a model substrate for the extraneuronal uptake of catecholamines. The accumulation of ISO when catechol-O-methyltransferase (COMT) (EC 2.1.1.6) was inhibited by 3',4'-dihydroxy-2-methylpropiophenone (U-0521) was decreased by ischemia to about 50% of the control value. Ischemia decreased the formation of 3-O-methyl-ISO, a major metabolite of ISO formed by COMT, to about 30% of that in the control hearts. The efflux of extraneuronally accumulated ISO in the heart with and without ischemia was measured. The diffusion constant calculated by the slope of the efflux rate of ISO or by the efflux rate divided by the amount of ISO remaining in the heart after ischemia was about 50% of the control. The experiments showed that ischemia suppressed the extraneuronal O-methylating system (extraneuronal uptake, COMT and diffusional flux) in the rat heart. Such suppression may lead to higher concentrations of local catecholamines in myocardial infarction.
Inoue
M
M
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Hifumi
K
K
Kurahashi
K
K
Fujiwara
M
M
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000032:analysis; D065098:Catechol O-Methyltransferase Inhibitors; D003327:Coronary Disease / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism*; D008297:Male; D008745:Methylation; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D065098:Catechol O-Methyltransferase Inhibitors; D002394:Catechol O-Methyltransferase; D007545:Isoproterenol