Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes.
The time courses of changes in cyclic nucleotide levels in monocytes have been studied. Histamine and prostaglandin E2 (PGE2) produced a rapid rise in cyclic AMP (peak 15 min) levels, which returned to normal within 4h, whereas cholera toxin, NaF and phosphodiesterase inhibitors produced slow sustained rises lasting over 24h. With the exception of isobutylmethylxanthine (10 mumol X 1(-1), none of these reagents altered cyclic GMP levels. alpha 1-Adrenergic and nicotinic cholinergic receptor-ligand interactions and imidazole produced rapid and relatively short-lived falls in cyclic AMP, and rises in cyclic GMP. In contrast, prostaglandin synthetase inhibitors produced delayed but more sustained falls in cyclic AMP but no rises in cyclic GMP. Agents that increased cyclic AMP decreased complement-component-C2 production, and those that decreased cyclic AMP increased C2 production. Agents that increased cyclic GMP alone (ascorbate, nitroprusside and prostaglandin F2 alpha) did not affect C2 production. Antigen-antibody complexes that stimulate C2 synthesis produced falls in cyclic AMP and rises in cyclic GMP similar to those produced by adrenergic and cholinergic ligands. Serum-treated complexes and anaphylatoxins, which inhibited C2 production, were associated with changes in cyclic AMP similar to those produced by histamine and PGE2. These data suggest that there are two transmembrane signals involved in the regulation of C2 production by monocytes. The inhibitory signal is adenylyl cyclase activation. The stimulatory signal is not so obvious, but may be Ca2+ influx, since the time courses of changes in cyclic nucleotides produced by agents that stimulate C2 synthesis are identical, and alpha 1-adrenergic agonists cause the formation of Ca2+ channels.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000706:Anaphylatoxins / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001337:Autonomic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003175:Complement C2 / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
D000706:Anaphylatoxins; D000936:Antigen-Antibody Complex; D001337:Autonomic Agents; D003175:Complement C2; D010726:Phosphodiesterase Inhibitors; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006152:Cyclic GMP