Studies on the mechanism of action of a new Ca-2+ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride in smooth and skeletal muscles.
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 muM) significantly inhibited equivalent responses of the rabbit aortic strip to KCl and noradrenaline. 3. TMB-8 (65 muM) produced no significant alteration in the extracellular space of the guinea-pig ileum as measured with [3H]-sorbitol. 4. The resting cellular Ca2+ influx as well as the resting 45Ca2+ efflux in the guinea-pig ileum preparation were significantly inhibited by TMB-8 (65 muM). 5. TMB-8 (5 muM and 50 muM) had no significant effect on the uptake of 45Ca2+ by the sarcoplasmic reticulum preparation of skeletal muscle; however, TMB-8 (5 muM) did significantly inhibit the caffeine (20 mM)-induced release of 45Ca2+ 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.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002132:Calcium Radioisotopes; D004048:Diethylamines / Q000494:pharmacology; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D002132:Calcium Radioisotopes; D004048:Diethylamines; D005707:Gallic Acid; D002118:Calcium