INHIBITION OF CATECHOLAMINE SECRETION AND CALCIUM EXCHANGE IN PERFUSED CAT ADRENAL GLANDS BY TETRACAINE AND MAGNESIUM

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Studies were carried out on cat adrenal glands perfused in situ to determine the effects of magnesium (Mg²⁺) and the local anesthetic, tetracaine, on catecholamine secretion and calcium movement. The presence of tetracaine (3 x 10^-4 M) or Mg²⁺(5 x 10^-3 M) profoundly inhibited (> 90%) the rate of catecholamine release when calcium (Ca²⁺) was subsequently added to Ca²⁺-free Locke's solution or to Ca²⁺-free Locke's solution containing 56 mM KCl. Inhibition by tetracaine was detectable at concentrations as low as 3 x 10^-6 M. The inhibitory effects of tetracaine and Mg²⁺ were reversed by raising the Ca²⁺ concentration in the perfusion fluid. Tetracaine, at concentrations as low as 1.5 x 10^-6 M, depressed the secretory response to acetylcholine (ACh). When tetracaine and magnesium were employed at concentrations which produced nearly equivalent inhibition of the ACh response, excess Ca²⁺(8 and 16 mM) was more effective in reversing the Mg²⁺-induced depression. Both tetracaine (3 x 10^-4 M) and Mg2+(5 x 10^-3 M) markedly depressed calcium exchange between the gland and the perfusate. Tetracaine also decreased Ca⁴⁵ uptake resulting from ACh stimulation. It is concluded that tetracaine and Mg²⁺ inhibit secretion by interfering with Ca²⁺ entry into the medullary chromaffin cells, presumably by an action at the cell membrane.