Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function.
Several microtubule-disrupting agents (colchicine, demecolcine, vinblastine, vincristine, podophyllotoxin, and nocodazole) have been shown to inhibit lymphocyte-mediated cytolysis. These agents also enhanced the prostaglandin E1-induced rise in cAMP levels in these cytolytic lymphocytes. Taxol, a natural product alkaloid that has been shown to enhance microtubule polymerization and to stabilize microtubules, antagonized both of these effects of the microtubule-disrupting agents in the cytolytic lymphocytes. Taxol also antagonized the enhancement of cAMP increases by colchicine in lymphocytes stimulated by 2-chloroadenosine, isoproterenol, and cholera toxin. The enhancement of the prostaglandin E1-induced cAMP response caused by treatment of the lymphocytes with either cytochalasin B or 3-deazaadenosine in the presence or absence of L-homocysteine was not antagonized by taxol. Taxol, colchicine, or the combination of these two agents did not affect ATP levels in cytolytic lymphocytes. These results support a modulatory role for microtubules in both the cytolytic process and the production of cAMP in these lymphocytes.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003078:Colchicine / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003703:Demecolcine / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D017239:Paclitaxel; D011458:Prostaglandins E / Q000494:pharmacology
D000470:Alkaloids; D011458:Prostaglandins E; D003571:Cytochalasin B; D000242:Cyclic AMP; D017239:Paclitaxel; D003078:Colchicine; D003703:Demecolcine