Permissive role of calcium in the inhibition of T cell mitogenesis by calmodulin antagonists.
The importance of Ca++ in the initiation of lymphocyte activation and mitogenesis has been supported by several studies. Because calmodulin functions as the intracellular mediator of the effects of Ca++, it likely plays a major role in the regulation of lymphocyte function. We have examined the effects of known calmodulin antagonists, the phenothiazines, on lectin-induced T cell mitogenesis and have shown a central role for Ca++ uptake in the expression of a phenothiazine-sensitive stage after lectin activation. The drug effects were observed only if the cells were previously activated by PHA or the ionophore A23187, and only in the presence of Ca++. These effects were restricted to a defined time period (5 hr) after lectin activation. The data support the concept that calmodulin is the target for the phenothiazine effects and demonstrate the permissive role of Ca++ in the mediation of these events.
D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood* / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010640:Phenothiazines / Q000378:metabolism / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D002147:Calmodulin; D010640:Phenothiazines; D010835:Phytohemagglutinins; D000001:Calcimycin; D002118:Calcium