Effect of Inhibitors of Neuronal and Extraneuronal Uptake on the Accumulation and Metabolism of ³H- l-Norepinephrine in Rabbit Aorta

Abstract

In the isolated adventitia of rabbit aorta, blockade of neuronal uptake decreased the accumulation and deamination of ³H-/-norepinephrine (³H- l-NE) whereas blockade of extraneuronal uptake decreased O-methylation. Thus most of the O-methylation occurs in the extraneuronal elements. In the isolated media, blockade of extraneuronal uptake decreased metabolism but not accumulation of ³H- l-NE. If NE metabolism was prevented by pretreatment with pargyline and U-0521, ³H- l-NE accumulation in the isolated media increased markedly and now inhibitors of extraneuronal uptake could decrease this accumulation of ³H- l-NE by the isolated media. Thus when MAO and COMT are intact, NE does not accumulate in the extraneuronal compartment containing these enzymes, probably because it is metabolized as fast as it enters the compartment. Since the level of ³H- l-NE in the isolated media exceeded the sorbitol space when MAO and COMT were intact, some ³H- l-NE must have accumulated in a compartment which does not contain these enzymes.