The binding of lipid and peptide chemotactic factors to cell surface receptors on polymorphonuclear leukocytes (PMNL) l initiates a series of intracellular biochemical events that lead to increased chemokinetic and chemotactic migra-

The binding of lipid and peptide chemotactic factors to cell surface receptors on polymorphonuclear leukocytes (PMNL) l initiates a series of intracellular biochemical events that lead to increased chemokinetic and chemotactic migration, aggregation, adherence, lysosomal degranulation, and production of superoxide anion (1-3). The rapid stimulation, by chemotactic factors, of phospholipid and protein methylation (4-6), arachidonic acid release (4, 5, 7), phosphatidyl inositol turnover (8-10), internal calcium release and influx of extracellular calcium (1 1, 12), glucose flux (13), and membrane depolarization (14) suggests that these events are closely coupled to receptor occupancy, yet little is known about the transductional process. Modulation by guanine nucleotides of the affinity of receptors for N-formylmethionyl peptides in membranes of human PMNL (15), and the activation, by N-formyl-methionyl-leucyl-phenylalanine (fMLP), of a GTPase activity in homogenates of PMNL (16) suggested that a guanine nucleotide-binding protein may participate in the transduction of signals from occupied receptors. Hormonally stimulated activation and inhibition of adenylate cyclase are mediated by coupling proteins, termed Gs and Gi, respectively, which have similar subunit structures and amino acid compositions (17); the a subunit of each protein contains a guanine nucleotide-binding site. Cholera toxin-induced ADP-ribosylation of the o~ subunit of Gs stabilizes Gs in the active state, and results in persistent activation of adenylate cyclase (18-20). A bacterial toxin isolated from Bordetella pertussis similarly catalyzes ADP-ribosylation of the a subunit of Gi, and, consequently, attenuates hormonal inhibition of adenylate cyclase activity (18, 19, 21). Although pertussis toxin treatment of rat mast cells does not alter