Inhibition of beta-adrenergic receptor-mediated signals by a synthetic peptide derived from the alpha subunit of the stimulatory G-protein.
The beta-adrenergic stimulation of adenylyl cyclase is mediated through the stimulatory G-protein (Gs). In this study, three synthetic peptides corresponding to different regions (amino acids 3-14, 72-86 and 325-337) of the alpha subunit of Gs (Gs-alpha) have been employed in competition assays in order to examine more closely the molecular basis of receptor-Gs-alpha interaction. The direct coupling between Gs and adenylyl cyclase was not influenced by any of these peptides and only the peptide representing residues 325-337 of Gs-alpha specifically inhibited beta-adrenergic receptor-mediated activation of Gs. Essentially the same results were obtained when testing beta-1- and beta-2-adrenergic receptors, which supports the notion that both these pharmacologically distinct receptor subtypes exploit at least one identical coupling domain within Gs-alpha for its activation.
Novotny
J
J
Institute of Sera and Vaccines (SEVAC), Srobarova 48, Prague, Czech Republic.
Gustafson
B
B
Ransnäs
L A
LA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D010446:Peptide Fragments; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases