ADENYLYL CYCLASE IN LUNG FROM HYPERSENSITIVE GUINEA-PIG DISPLAYS INCREASED RESPONSIVENESS TO GUANINE-NUCLEOTIDES AND ISOPRENALINE - THE ROLE OF THE G-PROTEINS G(S) AND G(I)

Basal adenylyl cyclase activity in lung membranes isolated from hypers ensitive guinea pigs was increased and more sensitive to stimulation b y isoprenaline, GTP and GppNHp when compared to adenylyl cyclase in lu ng membranes isolated from normal healthy guinea pigs. Maximal forskol in-stimulated adenylyl cyclase activity was unaltered. There was no ch ange in the immunological quantitative amounts of either alpha subunit s of the G proteins G(iII) and G(s) (G(o), G(iI) and G(iIII) were not present). Maximal pertussis-toxin- and cholera-toxin-catalyzed ADP-rib osylation of G(ialpha) and G(salpha) respectively were not significant ly altered. The addition of purified protein kinase C to isolated lung membranes resulted in the phosphorylation of the alpha subunit of G(s ) (stoichiometry was 0.53 mol of P-32 incorporated/mol of G(salpha)). Addition of protein kinase C to lung membranes isolated from hypersens itive guinea pigs was equally effective at catalysing the phosphorylat ion of the alpha subunit of G(s). GppNHp-stimulated and basal adenylyl cyclase activity was also enhanced in isolated tracheal smooth-muscle membranes from hypersensitive guinea pigs. These results suggest that hypersensitive reactions are associated with the improved coupling of the stimulatory G protein (G(s)) with adenylyl cyclase.