STUDIES ON THE MECHANISM OF ACTION OF A NEW Ca2+ ANTAGONIST, 8‐(N,N‐DIETHYLAMINO)OCTYL 3,4,5‐TRIMETHOXYBENZOATE HYDROCHLORIDE IN SMOOTH AND SKELETAL MUSCLES

Abstract

1 The rabbit aortic strip, guinea-pig ileum and rabbit skeletal muscle sarcoplasmic reticulum preparations were used to determine at which sites and in what manner 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate (TMB-8) interferes with Ca²⁺ availability in smooth and skeletal muscles. 2 TMB-8 (50 μM) significantly inhibited equivalent responses of the rabbit aortic strip to KCl and noradrenaline. 3 TMB-8 (65 μM) produced no significant alteration in the extracellular space of the guinea-pig ileum as measured with [³ H]-sorbitol. 4 The resting cellular Ca²⁺ influx as well as the resting ⁴⁵ Ca²⁺ efflux in the guinea-pig ileum preparation were significantly inhibited by TMB-8 (65 μM). 5 TMB-8 (5 μM and 50 μM) had no significant effect on the uptake of ⁴⁵ Ca²⁺ by the sarcoplasmic reticulum preparation of skeletal muscle; however, TMB-8 (5 μM) did significantly inhibit the caffeine (20 μ)-induced release of ⁴⁵ Ca²⁺ from this preparation. 6 It is concluded that TMB-8 reduces Ca²⁺ availability in smooth and skeletal muscles by stabilizing Ca²⁺ binding to cellular Ca²⁺ stores and thereby inhibits the release of this Ca²⁺ by contractile stimuli.