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.