Influence of TMB-8 on secretion of catecholamines from the perfused rat adrenal glands

Abstract

An attempt was made to investigate the effect of TMB-8 [3,4,5-trimethoxybenzoate-8 (N,N-diethylamino) octyl ester], which is known to be an inhibitor of intracellular Ca2+ release, on catecholamines (CA) secretion evoked by Ach, excess K+, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to clearify its mechanism of action. The pretreatment with a low dose of TMB-8 (10 μM) for 20 min led to marked inhibition in CA secretion evoked by Ach (5.32 mM), excess K+ (56 mM), DMPP (100 μM), McN-A-343 (100 μM) and BAY-K 8644 (10−5M). Caffeine-induced CA secretion was similar to that of control only during the first periods (0–3 min) but thereafter marked inhibition in CA secretion evoked by caffeine was observed during the rest periods up to 30 min. The increased moderate concentration of TMB-8 (30 μM) caused the result similar to that of 10 μM TMB-8. However, in adrenal glands preloaded with a high dose of TMB-8 (100 μM), CA releases evoked by Ach, excess K+, DMPP, McN-A-343 and caffeine were almost completely blocked by the drug. These experimental data demonstrate that TMB-8 may inhibit cholinergic receptor-mediated and also depolarization-dependent CA secretion, suggesting that these TMB-8 effects seem to be mediated through inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells as well as reducing the release of calcium from intracellular sources.