Molecular Pharmacology, Vol 11, 745-750, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

The Stimulation of Cathecholamine Release from Chromaffin Granules by Valinomycin

¹ Department of Physiology, Harvard Medical School, Boston, Massachusetts 02115

Valinomycin stimulates the release of catecholamine from isolated guinea pig adrenal medullary chromaffin granules incubated in vitro. Valinomycin-stimulated catecholamine release is dependent on the ionophore concentration and on the concentration of K⁺ in the incubation medium. In. 0.15 M KCl-5 mM Na·PO₄, pH 7.0, valinomycin at 1 µM increases catecholamine release about 5-fold. The finding that catecholamine release is accompained by the release of adenine nucleotides and of dopamine -hydroxylase from the chromaffin granules indicates that valinomycin induces the lysis of the granules. The effect of valinomycin on catecholamine release is also dependent upon the anions present in the incubation medium. The anions tested support valinomycin-stimulated catecholamine release in the order SCN^-, I^-, Br^- > Cl^- > acetate, F^-, isethionate. These data suggest that, in the presence of a membrane-permeable anion, valinomycin-mediated transport of K⁺ into chromaffin granules leads to the osmotic lysis of these granules.

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ACKNOWLEDGMENT We are grateful to Ms. Michi Chen for technical assistance.