Cyclosporine does not inhibit mitogen-induced inositol phospholipid degradation in mouse lymphocytes.
The degradation of phosphatidylinositol bisphosphate (PIP2) to diacylglycerol and inositol trisphosphate is elicited by ligand-receptor interactions in many cell types, and may be involved in the induction of cell growth. The mitogens concanavalin A and anti-immunoglobulin antibodies have previously been shown to induce degradation of PIP2 in mouse thymocytes and B cells, respectively. We have now investigated the effects of the immunosuppressive peptide cyclosporine (CS) on this response, since CS appears to inhibit an early step in lymphocyte activation by mitogens that induce PIP2 degradation and Ca2+ mobilization. We found that CS, at doses that completely abrogated the proliferative responses, did not affect the degradation of inositol phospholipids in either thymocytes or B cells. We therefore conclude that if PIP2 degradation is implicated in lymphocyte activation, then CS does not interfere with the second messenger production initiated by PIP2 breakdown, but rather with a later event(s) elicited by this pathway.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D003524:Cyclosporins; D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D003208:Concanavalin A; D004247:DNA