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Journal of Pharmacology And Experimental Therapeutics, Vol. 183, Issue 2, 284-297, 1972
Copyright © 1972 by American Society for Pharmacology and Experimental Therapeutics


THE EFFECT OF 6-HYDROXYDOPA ON PERIPHERAL ADRENERGIC NEURONS

RICHARD KOSTRZEWA 1 and DAVID JACOBOWITZ 1

1 Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

The time course of depletion and recovery of the norepinephrine (NE) content of several peripheral organs was studied after a single i.v. injection of 6-hydroxydopa (6-OHDOPA). The NE content of mouse cardiac ventricles, salivary glands, spleen and vas deferens was assayed and the adrenergic nerve plexus in various tissues was observed by the histochemical fluorescence method. 6-OHDOPA was capable of releasing NE from the ventricle, salivary glands and spleen in doses from 20 to 150 mg/kg i.v. The recovery of NE to control levels was complete in the salivary gland about two weeks after the 100 and 150 mg/kg doses, whereas the NE content of the ventricle did not return to control levels until three to six weeks after these dose levels. Perfusion of isolated hearts of 6-OHDOPA-treated rats with NE (1 µg/ml) for 10 minutes did not increase the number of adrenergic nerve terminals. A buildup of catecholamine fluorescence was observed in swollen preterminal axons of the rat iris. Pretreatment with a dopa decarboxylase inhibitor, L-agr-hydrazine methyldopa (MK-486) or 3-hydroxy-4-bromobenzyloxyamine phosphate (NSD-1055) or D- or L-amphetamine, desipramine or chlorpromazine prevented the depleting effects of 6-OHDOPA in the ventricle. It is suggested that 6-OHDOPA is converted to 6-hydroxydopamine which is then capable of causing actual destruction of noradrenergic nerve terminals.

Submitted on January 28, 1972
Accepted on June 27, 1972




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Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics.