The influence of monoamine oxidase and catechol-O-methyl transferase on the distribution of 3H-(+/-)-noradrenaline in rabbit aortic strips.

Abstract

1. Rabbit aortic strips were incubated with 1.18 μM 3H-(±)-noradrenaline for 30 min, and the accumulation of noradrenaline in the strips was measured as well as the total formation of metabolites. Some strips were exposed to 30 μM cocaine or 87μM corticosterone to inhibit neuronal and extraneuronal uptake, respectively. In some strips monoamine oxidase (MAO) and/or catechol-O-methyl transferase (COMT) was inhibited by pargyline and/or U-0521. Of the extraneuronal enzymes COMT is much more important than MAO; there is virtually no accumulation of noradrenaline in extraneuronal tissue when either COMT or both enzymes are intact. For adrenergic nerve endings, MAO is most important; very little or no COMT activity is associated with the nerve ending. When MAO is intact, there is virtually no axoplasmic accumulation of noradrenaline. Storage vesicles and MAO compete for axoplasmic noradrenaline. Neuronal and extraneuronal uptake and metabolism do not seem to compete for noradrenaline. 2. Other strips were incubated as described above and then washed out with amine-free solution for 240 min. When storage vesicles are intact, the long half time of the late neuronal efflux of radioactivity reflects the long half time for the conversion of “bound” to “free” amine; most of the free amine is then deaminated to dihydroxyphenyl glycol (DOPEG) when MAO is intact. Axoplasmically accumulated noradrenaline generates an efflux with a half time that is shorter than that for vesicular noradrenaline. A small proportion of the neuronal efflux of noradrenaline is taken up extraneuronally and converted to normetanephrine (NMN). When little or no noradrenaline accumulates in the strips during initial incubation, the strips lose some metabolites (DOPEG, NMN) quickly during wash out, while the acid metabolite, dihydroxymandelic acid (DOMA), leaves the tissue with a long half time; late efflux can then consist nearly exclusively of DOMA.