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  • Title: The kinetic characteristics of the extraneuronal Q-methylating system of the dog saphenous vein and the supersensitivity to catecholamines caused by its inhibition.
    Author: Paiva MQ, Guimarães S.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1984 Aug; 327(1):48-55. PubMed ID: 6493350.
    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)
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