POTENTIATION OF ADENYLYL-CYCLASE IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY CELL-ACTIVATING STIMULI

The isoprenaline-induced production of cAMP in human peripheral blood mononuclear cells (PBMC) was potentiated significantly by incubating P BMC with isoprenaline in the presence of phytohaemagglutinin (PHA), Co ncanavalin A (Con A) or A23187. This potentiation, that proved to be d ependent on the concentration of PHA, Con A or A23187, increased the m aximal response but did not cause a change in the potency of isoprenal ine. Potentiation could not be induced by the phorbol ester phorbolmyr istate acetate, suggesting that protein kinase C-dependent pathways ar e not likely to be involved in potentiation of adenylyl cyclase. Poten tiation could be inhibited by chelating extracellular Ca2+ with EGTA a nd also by N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamine, an inhib itor of calmodulin. Potentiation could not be induced by preincubation of PBMC with PHA, suggesting that transient biochemical changes are i nvolved. It was concluded from these results that potentiation in PBMC probably involves the activation of Ca2+/calmodulin-dependent adenyly l cyclase subtypes. Potentiation of the adenylyl cyclase activity coul d be an important physiological mechanism in vivo preventing cells fro m becoming ''over stimulated''.