The termination of action of catecholamines in the isolated venous tissue of the dog

Summary The termination of responses to noradrenaline and adrenaline was studied, using the oil immersion technique, in helically cut strips obtained from the lateral saphenous vein of the dog. Inhibitors of catechol-O-methyltransferase (tropolone), monoamine oxidase (iproniazid) or neuronal uptake (cocaine and imipramine-N-oxide) slowed the relaxation rate of strips contracted by noradrenaline or adrenaline (10^–5 and 10^–6 M) and immersed in oil. From these experiments it is concluded that, at the concentrations used, oxidative deamination represents the major inactivation pathway for both catecholamines, and that O-methylation plays only a minor role in the disposition of the amines; however, the inactivation of adrenaline is more dependent on catechol-O-methyltransferase than that of noradrenaline. Tissue uptake and storage occupied an intermediate position between the enzymatic pathways referred to: iproniazid inhibited 79%, cocaine 54% and tropolone 27% of the inactivation capacity when 10^–5 M noradrenaline was used. However, the combination of the three drugs inhibited only 88% of the inactivation capacity. This is due to the marked overlap of the effects of cocaine and iproniazid, which is attributed to the blockade by cocaine of the access of the amine to intraneuronal sites of oxidative deamination.Cocaine caused marked potentiation of responses to noradrenaline and moderate prolongation of relaxation time, while iproniazid, which had much more marked effects on the termination of action of noradrenaline, induced only a slight augmentation of the contractile responses. It is concluded that potentiation is an unreliable index of altered disposition of noradrenaline in this preparation.Experiments with perfused venous segments showed that, following the concentration gradient, noradrenaline diffuses freely through the vein wall, and that there is no marked difference in responses to adventitial or intimal application of the amine. Radioautographic studies gave evidence of two different types of accumulation (neuronal and extraneuronal), which appeared to be in equilibrium.Supported in part by a grant from III Plano de Fomento (Actividades, 1970).