Adenylyl cyclase in lung from hypersensitive guinea pig displays increased responsiveness to guanine nucleotides and isoprenaline: the role of the G proteins Gs and Gi.
Basal adenylyl cyclase activity in lung membranes isolated from hypersensitive guinea pigs was increased and more sensitive to stimulation by isoprenaline, GTP and GppNHp when compared to adenylyl cyclase in lung membranes isolated from normal healthy guinea pigs. Maximal forskolin-stimulated adenylyl cyclase activity was unaltered. There was no change in the immunological quantitative amounts of either alpha subunits of the G proteins GiII and Gs (G(o), GiI and GiIII were not present). Maximal pertussis-toxin- and cholera-toxin-catalyzed ADP-ribosylation of Gi alpha and Gs alpha respectively were not significantly altered. The addition of purified protein kinase C to isolated lung membranes resulted in the phosphorylation of the alpha subunit of Gs (stoichiometry was 0.53 mol of 32P incorporated/mol of Gs alpha). Addition of protein kinase C to lung membranes isolated from hypersensitive guinea pigs was equally effective at catalysing the phosphorylation of the alpha subunit of Gs. 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 (Gs) with adenylyl cyclase.
Grady
M
M
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Stevens
P A
PA
Pyne
S
S
Pyne
N
N
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000201:enzymology*; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010047:Ovalbumin; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014132:Trachea / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D006150:Guanine Nucleotides; D010566:Virulence Factors, Bordetella; D006165:Guanylyl Imidodiphosphate; D010047:Ovalbumin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate