Abstract
Effects of diltiazem on catecholamine (CA) release evoked by several secretagogues were investigated in cat adrenal glands perfused in situ with Locke solution. All compounds were introduced into the perfusion medium. It was found that the release of CA stimulated by either acetylcholine (ACh) (10-4M) or high K+ (56mM) was reduced by approximately 50 and 90% in the presence of 10-5 and 10-4M diltiazem respectively, while diltiazem at 10-6M exhibited little or no influence on the Ca release. In addition, diltiazem at a concentration of 10-6M or higher produced a dose-related decrease in the CA release evoked by introduction of CaCl2 (2.2mM) into nomically Ca2+-free perfusion medium. On the other hand, removal of Na+ from the perfusion medium (osmolarity was adjusted with osmotically equal amount of sucrose) caused an increase in release of CA from the glands. Diltiazem (10-5M or higher) also reduced this CA release, but its activity was weaker than those found in experiments with ACh, high K+, and Ca2+. In all cases, the effects were reversible on washout. On the contrary, diltiazem, even at a higher concentration of 10-4M, exhibited no inhibitory effect on the release of CA induced by acet-aldehyde (3×10-3M). It was suggested that diltiazem, through its Ca2+-antagonistic action, may reduce the evoked CA release which depends on extracellular Ca2+.
