title: Effects of the C-terminal peptide of the alphaS subunit of the G protein on the regulation of adenylyl cyclase and protein kinase A activities by biogenic amines and glucagon in mollusk and rat muscles.
abstract: The C-terminal parts of the a subunits of heteromeric G proteins play an important role in the functional linkage of G proteins with receptors of the serpentine type. The present report describes studies of the effects of the C-terminal octapeptide 387-394 of the alphaS subunit of the mammalian G protein on the transmission of the hormonal signal via the hormone-sensitive adenylyl cyclase signal system, whose major components are receptors of the serpentine type, G proteins, and the enzymes adenylyl cyclase and protein kinase A. The peptide synthesized here, 387-394 amide (10(-7) - 10(-4) M), dose-dependently decreased adenylyl cyclase and protein kinase A activities stimulated by serotonin and glucagon in smooth muscle from the freshwater bivalve mollusk Anodonta cygnea and by the beta agonist isoproterenol in rat skeletal muscle. At a concentration as low as 10(-7) M, the peptide released potentiation of the stimulatory effects of hormones on adenylyl cyclase activity due to the non-hydrolyzable guanine nucleotide analog Gpp[NH]p. At the same time, it had almost no effect on the stimulation of adenylyl cyclase activity by non-hormonal agents (NaF, Gpp[NH]p, and forskolin). The inhibitory effects of hormones on adenylyl cyclase and protein kinase A activities persisted in the presence of the peptide. Our data demonstrate the importance of the C-terminal part of the alphaS subunit of the stimulatory G protein for its functional linkage with receptors of the serpentine type and throw light on the molecular mechanisms of the interactions between G proteins and receptors.
authors.affiliation: I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia.
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
authors.forename: V I
authors.initials: VI
authors.lastname: Korol'kov
authors.forename: S A
authors.initials: SA
authors.lastname: Plesneva
authors.forename: L A
authors.initials: LA
authors.lastname: Kuznetsova
authors.forename: M N
authors.initials: MN
authors.lastname: Pertseva
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D044385:GTP-Binding Protein alpha Subunits / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008974:Mollusca; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D015306:Biogenic Monoamines; D044385:GTP-Binding Protein alpha Subunits; D010455:Peptides; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D005934:Glucagon; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D007545:Isoproterenol