Neutrophils (PMNs) treated with cyclic AMP elevating agents were evaluated for to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B(4) (LTB(4)). Prostaglandin E(1) (PGE(1)) and isoproterenol, increased PMN cyclic in AMP production and inhibited chemotaxis to both FMLP and LTB(4). In contrast, forskolin, which activates adenylate cyclase directly, inhibited chemotaxis to FMLP but not to LTB(4). The phosphodiesterase inhibitor, 3-isobutyl-1 -methylxanthine (IBMX), was, required for inhibition of PMN chemotaxis to FMCP by forskolin, PGE,, and isoproterenol. Isoproterenol and PGE, inhibited PMN chemotaxis to LTB4 in the absence of IBMX and chemotaxis was further inhibited in the presence of IBMX. PMN cyclic AMP levels were stimulated 2-3-fold with isoproterenol, 6-10-fold with PGE1, and 5-7-fold with forskolin over basal levels in the presence of IBMX. These observations demonstrate that total cellular cyclic AMP concentration is not-correlated with inhibition of PMN chemotaxis to all stimuli; forskolin, which increased cyclic AMP 5-7-fold over basal levels, did not inhibit chemotaxis to LTB4, Whereas isoproterenol, which increased cyclic AMP only 2-3-fold over basal levels, inhibited -chemotaxis to LTB4- PMN cyclic AMP extrusion was determined under basal conditions and in the presence of PGE1, isoproterenol, or forskolin. PMNs extruded cyclic AMP under all conditions examined. Results of this study were presented at the 1990 FASEB Meetings, April 1-5, 1990 in Washington, D.C. A manuscript describing this work has been submitted.
