title: Inhibition of adenylyl cyclase by Gi alpha.
abstract: Evidence suggests that both alpha and beta gamma subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) inhibit adenylyl cyclase. Although type I adenylyl cyclase is inhibited directly by exogenous beta gamma, inhibition of adenylyl cyclase by Gi alpha has not been convincingly demonstrated in vitro. Concentration-dependent inhibition of adenylyl cyclases by purified Gi alpha subunits is described. Activated Gi alpha but not G(o) alpha was effective, and myristoylation of Gi alpha was required. The characteristics of the inhibitory effect were dependent on the type of adenylyl cyclase and the nature of the activator of the enzyme. The concentrations of Gi alpha required to inhibit adenylyl cyclase were substantially higher than those normally thought to be relevant physiologically. However, analysis indicates that these concentrations may be relevant and reasonable.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
authors.forename: R
authors.initials: R
authors.lastname: Taussig
authors.forename: J A
authors.initials: JA
authors.lastname: Iñiguez-Lluhi
authors.forename: A G
authors.initials: AG
authors.lastname: Gilman
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D009036:Moths; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D009227:Myristic Acids; D011994:Recombinant Proteins; D019814:Myristic Acid; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases