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Journal of Pharmacology And Experimental Therapeutics, Vol. 156, Issue 1, 31-38, 1967
Copyright © 1967 by American Society for Pharmacology and Experimental Therapeutics

THE EFFECT OF DRUGS ON THE RELEASE OF NOREPINEPHRINE-H3 FROM CENTRAL NERVOUS SYSTEM TISSUES BY ELECTRICAL STIMULATION IN VITRO

Ross J. Baldessarini 1 and Irwin J. Kopin 2

1 Laboraetory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland
2 Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

Slices of mammalian brain and peripheral adrenergically innervated tissues accumulate norepinephrine-H3 when incubated in a physiologic medium with dopamine-H3 or norepinephrine-H3. When these tissues are subjected to mild electrical stimulation of short duration, which is associated with depolarization of nerve membranes, a striking increase in the rate of efflux of the exogenous catecholamines and of the endogenously synthesized radioactive norepinephrine occurs. This release does not appear to be due to heating or to increased diffusion and does not occur when slices are prepared from chronically denervated tissue. Similar release of norepinephrine-H3 is obtained when depolarization is induced by increasing the K+ concentration of the superfusion medium. Electrically stimulated release of norepinephrine from brain slices is markedly inhibited in the presence of reduced concentrations of Ca++ and is significantly diminished when small amounts of chlorpromazine or desmethylimipramine are present in the medium. A similar inhibition of release is seen in heart slices with reduced concentrations of Ca++, or with thiopental in the medium.

Submitted on July 25, 1966
Accepted on November 7, 1966




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