The effect of partial inhibition of monoamine oxidase on the steady-state rate of deamination of 3H-catecholamines in two metabolizing systems

Publisher Website
Google Scholar
Abstract
Two different “deaminating systems” were compared (i.e., intact tissues in which an uptake process translocates the 3H-catecholamine from the extracellular space to the intracellular MAO): 1) the adrenergic nerve endings of the rat vas deferens exposed to 10 nmol/l 3H-(−)-noradrenaline, and 2) the extraneuronal deaminating system of the rat heart perfused with 50 nmol/l 3H-(−)-adrenaline. Vesicular uptake and COMT were inhibited. In both systems MAO was partially inhibited by pargyline, and the steady-state tissue content of the 3H-catecholamine was determined as well as the steady-state rate of deamination. Rat vas deferens (preincubated with 10–40 nmol/l pargyline for 30 min). Inhibition of neuronal MAO caused not more than a moderate decrease of the steady-state rate of deamination of 3H-(−)-noradrenaline, but the steady-state tissue content was greatly increased. Determinations of the activity of MAO in homogenates of vasa deferentia showed that preincubation with 10 and 20 nmol/l pargyline inhibited the enzyme by 80 to 95%. Rat heart (of animals pretreated with 1 to 30 mg/kg pargyline). Inhibition of extraneuronal MAO caused a steep decline of the steady-state rate of deamination of 3H-(−)-noradrenaline but only a small rise in the steady-state tissue content. The decisive difference between the two deaminating systems lies in the fact that the ratio “k mao/k out” (where the two k-values characterize the activity of the unsaturated intracellular MAO and the ability of the 3H-catecholamine to leave the relevant cells, respectively) is much higher for the neuronal deaminating system exposed to 3H-(−)-noradrenaline than for the extraneuronal deaminating system exposed to 3H-(−)-adrenaline. Whenever this ratio is high, pronounced (but incomplete) inhibition of MAO results in a very pronounced increase in the intracellular steady-state 3H-amine concentration (during exposure of the tissue to a 3H-catecholamine); as far as the steady-state rate of deamination is concerned, the pronounced rise in substrate concentration largely masks the pronounced degree of inhibition of MAO. When, however, the ratio is close to unity, inhibition of MAO fails to result in any pronounced increase in the intracellular steady-state 3H-amine concentration; as a consequence, any pronoumced inhibition of MAO is then reflected by a pronounced decrease of the steady-state rate of deamination. From the present results it is concluded that, in experiments with intact tissues, the degree of inhibition of MAO cannot be derived from measurements of rates of deamination of 3H-catecholamines.

This publication has 28 references indexed in Scilit: