ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. A possible role of the toxin substrate in Ca2+-mobilizing biosignaling.
Guinea pig neutrophils were maintained for 4 h in culture medium containing [3H]arachidonic acid for the purpose of labeling cellular phospholipids. A short incubation of these cells with a chemotactic peptide resulted in rapid generation of superoxide anion, increased release of arachidonic acid (and small amounts of its metabolites) due to breakdown of phospholipids, and enhanced Ca2+ influx. These metabolic responses of cells to the chemotactic peptide were markedly suppressed when the cells had been exposed to islet-activating protein (IAP), pertussis toxin, during 4-h culture, as a result of ADP-ribosylation of a membrane Mr = 41,000 protein. This IAP-induced suppression was far greater than the maximal suppression observed with cellular cAMP increases; the action of IAP on neutrophils was not solely cAMP dependent. In contrast to the responses to the chemotactic peptide, similar responses of neutrophils to A23187, a Ca2+ ionophore, were not affected by the prior treatment of the cells with IAP. It is proposed that in neutrophils the IAP substrate, which is a subunit of the guanine nucleotide regulatory protein involved in adenylate cyclase inhibition in a variety of other cell types, plays an essential role in the Ca2+-mobilizing receptor-mediated signal transduction system, conceivably in processes proximal to Ca2+ gating.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D037361:Adenylate Cyclase Toxin; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001427:Bacterial Toxins / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D037342:Pertussis Toxin; D013481:Superoxides / Q000097:blood; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001095:Arachidonic Acids; D001427:Bacterial Toxins; D008565:Membrane Proteins; D009702:Nucleoside Diphosphate Sugars; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D000246:Adenosine Diphosphate Ribose; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine