Islet-activating protein inhibits leukotriene D4- and leukotriene C4- but not bradykinin- or calcium ionophore-induced prostacyclin synthesis in bovine endothelial cells.
Incubation of the bovine endothelial cell line, CPAE, with leukotriene D4, leukotriene C4, bradykinin, or the calcium ionophore A23187 results in the release of arachidonic acid metabolites including 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment of these cells with the pertussis toxin islet-activating protein (IAP) results in a dose-dependent inhibition of the release of arachidonic acid metabolites and prostacyclin in response to leukotriene D4 and leukotriene C4. In contrast, similar responses evoked by bradykinin or ionophore were not significantly altered by the IAP pretreatment of the cells. IAP in the presence of [32P]NAD specifically [32P]ADP-ribosylates a 41-kDa protein in membranes prepared from CPAE cells. Pretreatment of the intact cells with IAP resulted in a dose-dependent inhibition of subsequent 32P labeling of the toxin substrate in the membranes and correlates with the uncoupling of the leukotriene responses. These results suggest that the 41-kDa IAP substrate, presumably a guanine nucleotide regulatory protein, mediates the response of CPAE cells to leukotriene D4 and leukotriene C4, but not to bradykinin or the calcium ionophore.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004727:Endothelium / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D037342:Pertussis Toxin; D013189:SRS-A / Q000037:antagonists & inhibitors*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D001095:Arachidonic Acids; D008565:Membrane Proteins; D013189:SRS-A; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D037342:Pertussis Toxin; D001920:Bradykinin