Differentiation of calcium antagonists with respect to their effects in normal and skinned taenia caeci preparations.
In taenia preparations, depolarized by a K+-rich medium, Ca2+ caused contraction and cinnarizine (0.4-100 microM), trifluoperazine (2-100 microM) and verapamil (0.02-10 microM) caused concentration-dependent antagonism of Ca2+, displacing the Ca2+ log concentration-effect curve to the right and depressing the maximal response. Equieffective (IC75) antispasmogenic concentrations were selected. The antispasmogenic effects of verapamil were readily offset by removing the drug from the bathing fluid but those of the other drugs were not. The calcium antagonists (antispasmogenic IC75) were then tested for spasmolytic activity in tissues generating tension in response to the EC80 of Ca2+. Verapamil was more effective in producing spasmolysis than cinnarazine or trifluoperazine. In skinned taenia preparations, verapamil (100 microM) did not inhibit Ca2+-induced contractions. High concentrations of cinnarizine (100 microM) and trifluoperazine (100 microM) inhibited Ca2+-induced activation of the contractile proteins. However, antispasmogenic IC75s from intact taenia were not able to produce this effect on skinned preparations. It is concluded that there are differences between calcium antagonists. The action of verapamil on intact taenia is mainly exerted on the plasma membrane. Cinnarizine and trifluoperazine act both on the plasma membrane and upon the intracellular contractile machinery.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology; D002936:Cinnarizine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D010276:Parasympatholytics; D014268:Trifluoperazine; D002936:Cinnarizine; D014700:Verapamil; D002118:Calcium