Pertussis toxin inhibits the N-formyl-MetLeu-Phe (fMet-Leu-Phe) mediated human neutrophil functions of enzyme release, superoxide generation, aggregation, and chemotaxis. As pertussis toxin modifies the GTP binding receptor-regulatory protein "N1," the association of the fMetLeu-Phe receptor with such a protein was further examined in purified neutrophil plasma membranes. Both fMet-Leu-Phemediated guanine nucleotide exchange and nucleotide-mediated regulation of the fMet-Leu-Phe receptor are inhibited by pertussis toxin. In addition, membrane pretreatment with pertussis toxin abolishes the fMet-Leu-Phe-mediated inhibition of adenylate cyclase. Actions of pertussis toxin are due to the ADP-ribosylation of a single subunit at 41 kDa in the neutrophil plasma membrane, which comigrates on NaDodSO4 gels with the N. GTP-binding protein in the platelet plasma membrane. Our results suggest that (i) the fMet-Leu-Phe receptor is associated with a N. GTP regulatory protein, and (it) a fMetLeu-Phe-N; complex is important in the control of several neutrophil functions, probably involving multiple transduction systems, including adenylate cyclase.

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