title: The kinetic characteristics of the extraneuronal Q-methylating system of the dog saphenous vein and the supersensitivity to catecholamines caused by its inhibition.
abstract: The "half-saturating outside concentration" and the Vmax of the extraneuronal O-methylating system of the dog saphenous vein were determined in vitro for 3 catecholamines: isoprenaline, adrenaline and noradrenaline. Strips pretreated with 1 mmol/l pargyline were exposed to 30 mumol/l cocaine for 30 min before and during the 30 min incubation with the amines. Two methods were used to reach our aims: a) the classical one in which the 3H-O-methylated metabolites formed from a mixture of unlabelled and labelled amine were determined by using final concentrations of the substrate ranging from 0.2 and 12.8 mumol/l and b) an indirect one in which 0.2 mumol/l 3H-(+/-)-isoprenaline was used to assess the extraneuronal O-methylation of the tracer amine, and then those concentrations of unlabelled amines were determined which reduce the O-methylation of 3H-(+/-)-isoprenaline by 50% (IC50). The "half-saturating outside concentrations" and the Vmax obtained by the first method were: 1.3, 2.5 and 3.4 mumol/l and 241, 317 and 294 pmol/g/min for 3H-(+/-)-isoprenaline, 3H-(+/-)-adrenaline and 3H-(-)-noradrenaline, respectively. The IC50s obtained by the second method used were: 1.1, 0.6, 0.7 and 1.4 mumol/l for (+/-)-isoprenaline, (-)-isoprenaline, (-)-adrenaline and (-)-noradrenaline, respectively. It was observed that the contraction of the strips caused by adrenaline and noradrenaline distorted IC50 values. In the presence of 1 mumol/l phentolamine the IC50 for adrenaline and noradrenaline was about 2.5 times higher than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D007700:Kinetics; D008745:Methylation; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D014316:Tritium
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D011427:Propiophenones; D014316:Tritium; D010656:Phenylephrine; C006104:U 0521; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine