Phorbol Myristate Acetate Stimulation of Lymphocyte Guanylate Cyclase and Cyclic Guanosine 3′:5′-Monophosphate Phosphodiesterase and Reduction of Adenylate Cyclase

摘要: Abstract Human peripheral blood lymphocytes incubated with the tumor promoter and T-cell mitogen phorbol-12-myristate-13-acetate (PMA) had elevated cyclic guanosine 3′:5′-monophosphate (cyclic GMP) levels activities of guanylate cyclase GMP phosphodiesterase reduced activity adenylate cyclase. No changes occurred in adenosine or phosphodiesterase. Cyclic increased a bimodal fashion corresponding to brisk rise at 1 min both membrane soluble cyclases second increase 20 60 Decreases were similar for basal isoproterenol- NaF-stimulated activity. The magnitude these increasing concentrations PMA from 0.01 10 µg/ml, while effects on lymphocyte proliferation progressively 0.001 µg/ml. series phorbol diesters consistent their relative mitogenesis promotion. Because mononuclear cell populations are heterogeneous, cause effect relationships between enzyme biological responses cannot now be ascertained. None PMA-induced significantly affected by inhibition macromolecular synthesis omitting Ca 2+ preincubation medium. increases markedly inhibited intracellular antagonist methoxyverapamil but not [ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid. stimulation was prevented arachidonic acid lipoxygenase inhibitors 15-hydroxyeicosatetraenoic nordihydroguaiaretic Increases reduction less susceptible inhibitors. These results suggest that stimulates -dependent process which, membrane, involves one more metabolites different mechanisms may account alterations other nucleotide-metabolizing activities.