Role of ADP-ribosylation in endothelial signal transduction and prostacyclin production.

ADP-ribosylation of proteins by the enzymatic transfer of ADP-ribose from NAD has been implicated in a number of biological processes. We report that inhibitors of ADP-ribosylation, most notably the novel inhibitor of arginine specific cellular mono(ADP-ribosyl) transferase, meta-iodobenzylguanidine (MIBG) as well as nicotinamide, L-arginine methyl ester (LAME) and guanyltyramine, inhibit histamine-induced endothelial production of inositol phosphates, release of arachidonic acid and production of prostacyclin (PGI2). Those same responses were unaffected by MIBG when triggered by thrombin or leukotriene C4. These findings suggest that ADP-ribosylation serves a role in histamine-induced production of prostacyclin and imply differences in transduction pathways employed by the different agonists.