Disease relevance of COMT

• Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias [1].
• Tolcapone (T) is a novel catechol-O-methyltransferase (COMT) inhibitor recently introduced for the treatment of Parkinson's disease [2].

High impact information on COMT

• Evidence for the beta-adrenergic receptor regulation of membrane-bound catechol-O-methyltransferase activity in myocardium [3].
• These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine [1].
• The inhibition of catechol-O-methyltransferase by U-0521 caused a decrease of NMN and OMDA during the spontaneous outflow, and a shift from O-methylation to deamination of NE [4].
• In these experiments, 12 mumol/l cocaine (to inhibit uptake1), 41 mumol/l hydrocortisone (to reduce uptake2) and 50 mumol/l U-0521 (to inhibit COMT) were present during the perifusion [5].
• Identification of major metabolites of the catechol-O-methyltransferase inhibitor nitecapone in the rat and dog [6].

Biological context of COMT

• Breed differences in genotype and allele frequency of catechol O-methyltransferase gene polymorphic regions in dogs [7].
• Metabolites of nitecapone [3-(3,4-dihydroxy-5-nitrobenzylidene)-2,4-pentanedione], a potent catechol-O-methyltransferase inhibitor with gastroprotective and antiulcerogenic effects, were isolated by extraction and HPLC from dog and rat urine after enzymatic hydrolysis and as glucuronic acid and sulfate conjugates [6].

Anatomical context of COMT

• It is concluded that COMT is related to smooth muscle cells in this tissue [8].
• Our results strongly support the view that alpha-adrenoceptors are in close contract with the nerve endings and beta-adrenoceptors are in close proximity of COMT in a vessel with the nerve endings evenly distributed throughout the media [9].
• Effect of catechol-O-methyl-transferase (COMT) inhibition on the vascular and metabolic responses to noradrenaline, isoprenaline and sympathetic nerve stimulation in canine subcutaneous adipose tissue [10].
• Dog splenic artery strips were incubated with [3H]NA after inhibition of catechol-O-methyl-transferase (COMT) and of extraneuronal uptake [11].
• Effect of cooling on COMT activity in canine saphenous vein homogenates determined by a micro radioenzymatic assay [12].

Associations of COMT with chemical compounds

• Thus, the excretion of dopamine by the cat kidney is linked to an inactivation by the kidney enzymes MAO and COMT [13].
• The activity of COMT was assayed with the method of Axelrod (1962, Methods in Enzymology, Vol. 5. Academic Press, New York) in the presence of epinephrine bitartrate as a substrate [14].
• FS-32 tended to produce an increase in chatecholamine content in the brain without MAO or COMT inhibitory activity [15].
• Cocaine was used to inhibit neuronal uptake and COMT was blocked with 3,4-dihydroxy-2-methyl propiophenone [16].
• Using the oil immersion technique, the role of neuronal uptake, monoamine oxidase and COMT in the inactivation of 2 concentrations (0.23 and 2.3 mumol/l) of noradrenaline and adrenaline was determined by the prolongation of the inactivation time caused by cocaine (12 mumol/l), pargyline (1 mmol/l) and U-0521 (50 mumol/l), respectively [17].

Analytical, diagnostic and therapeutic context of COMT

• Coronary ligation for 24 hours resulted in a decrease in the level of epinephrine and an increase in the level of dopamine in the adrenal medulla, and also resulted in an increase in the activities of the phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase, and catechol-O-methyltransferase [18].

References