Mapping of β‐adrenoceptor coupling domains to Gs‐protein by site‐specific synthetic peptides

• Published in: FEBS letters 1989-08, Vol.254 (1-2), p.89-93
• Main Authors: Palm, Dieter, Münch, Gerald, Dees, Christian, Hekman, Mirko
• Format: Article
• Language: English
• Subjects: 1,4-dithiothreitol; Adenylyl Cyclases - analysis; Adrenoceptor, β; Animals; Binding Sites; Biological and medical sciences; Cell receptors; Cell structures and functions; Coupling domain; DTT; Enzyme Activation - drug effects; Erythrocyte Membrane - drug effects; Erythrocyte Membrane - metabolism; Fundamental and applied biological sciences. Psychology; Gs-protein; GTP-Binding Proteins - analysis; GTPγS; guanine nucleotide-binding protein mediating stimulation of adenylate cyclase; Guanosine Triphosphate - pharmacology; guanosine-5′-O-(3-thiotriphosphate); Isoproterenol - pharmacology; Molecular and cellular biology; Molecular Structure; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); N-methylpyrrolidone; NMP; Peptide Mapping; Peptides - chemical synthesis; Propranolol - pharmacology; Receptors, Adrenergic, beta - analysis; Receptors, Adrenergic, beta - physiology; Synthetic peptide; TFA; trifluoroacetic acid; Turkeys
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(89)81015-4

Peptides corresponding to the known sequence of turkey erythrocyte β1‐adrenergic receptor were synthesized and the effects on receptor‐mediated cyclase activation were measured. Peptides corresponding to the first and second intracellular loops (T61‐71 and T138‐159) inhibited at micromolar concentrations the hormone‐dependent cyclase activation in turkey erythrocyte membranes. In contrast, the peptide corresponding to the C‐terminal part of the third intracellular loop (T284‐295) increased the cyclase activity in a hormone‐independent manner. Peptides T338‐353 and T2‐10 and a number of synthetic peptides unrelated to the β‐adrenoceptor had no effect.