Coupling of the guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin. A possible role of the toxin substrate in Ca2+-mobilizing receptor-mediated signal transduction.

摘要: A chemotactic peptide stimulated the high-affinity GTPase activity in membrane preparations from guinea pig neutrophils. The enzyme stimulation was inhibited by prior exposure of membrane-donor cells to islet-activating protein (IAP), pertussis toxin, or direct incubation with its A-protomer (the active peptide) presence NAD. affinity for binding receptors lowered guanyl-5'-yl beta, gamma-imidodiphosphate (Gpp(NH)p) reflecting coupling guanine nucleotide regulatory absence Gpp(NH)p lower, but not, A-protomer-treated membranes than nontreated membranes. inhibitory adenylate cyclase (Ni) purified rat brain, and reconstituted into IAP-treated cells. reconstitution very effective increasing formyl-Met-Leu-Phe-dependent due increase. half-maximal concentration IAP inhibit comparable that toxin cellular arachidonate-releasing response which well correlated ADP-ribosylation a Mr = 41,000 (Okajima, F., Ui, M. (1984) J. Biol. Chem. 259, 13863-13871). It is proposed substrate, Ni, couples receptor mediates responses neutrophils, as it inhibition many other cell types.