Inhibition of Calcium Uptake, Sodium Uptake, and Catecholamine Secretion by Methoxyverapamil (D600) in Primary Cultures of Adrenal Medulla Cells

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Abstract
The Ca-entry antagonist D600 (methoxyverapamil) inhibited nicotine- and veratridine-induced 45Ca2+ uptake, 22Na+ uptake, and catecholamine secretion in primary cultures of bovine adrenal medulla cells. Inhibition of nicotine-induced effects occurred at D600 concentrations .apprx. 3- to 10-fold lower than those needed to produce similar inhibition of veratridine-induced effects. Inhibition of the veratridine-induced effects was competitive, but inhibition of the nicotine-induced effects was not competitive. D600, in addition to blocking slow Ca2+ channels and tetrodotoxin-sensitive Na+ channels also blocks nicotine transmission, possibly either by noncompetitively inhibiting the interaction of nicotine with the receptor binding site or by blockade of the receptor-associated ion conductance channel.