Abstract
The various receptors for catecholamines, termed adrenergic receptors, represent excellent model systems for the study of receptor-mediated transmembrane signaling systems because of their ubiquity, coupling to well-defined effector mechanisms, and the clinical importance of drugs which interact with them. The β 1 and β 2-adrenergic receptors stimulate adenylyl cyclase via the guanine nucleotide regulatory protein Gs. The α 2-adrenergic receptors inhibit adenylyl cyclase via Gi. The α 1-adrenergic receptors stimulate hydrolysis of polyphosphoinositides by activating phospholipase C, thus generating inositol triphosphate and diacylglycerol. Each of these systems is in turn analogous to the retinal light transduction system which consists of the prototypic receptor rhodopsin, a G-protein transducin, and an effector enzyme, which is a cyclic GMP phosphodiesterase.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Benovic JL, Pike LJ, Cerione RA, Staniszewski C, Yoshimasa T, Codina J, Birnbaumer L, Caron MG & Lefkowitz RJ (1985) Phosphorylation of the mammalian β-adrenergic receptor by cAMP-dependent protein kinase: regulation of the rate of receptor phosphorylation and dephosphorylation by agonist occupancy and effects on the coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. J Biol Chem 260: 7094–7101
Benovic JL, Kuhn H, Weyand I, Codina J, Caron MG & Lefkowitz RJ (1987a) Functional desensitization of the isolated β-adrenergic receptor by the β-adrenergic receptor kinase: potential role of the analog of the retinal binding protein arrestin (48KDa). Proc Natl Acad Sci USA 84: 8879–8882
Benovic JL, Mayor F Jr, Staniszewski C, Lefkowitz RJ & Caron MG (1987b) Purification and characterization of the β-adrenergic receptor kinase. J Biol Chem 262: 9026–9032
Bouvier M, Hausdorff WP, DeBlasi A, O’Dowd BF, Kobilka BK, Caron MG & Lefkowitz RJ (1988) Removal of phosphorylation sites from the β.,-adrenergic receptor delays onset of agonist-promoted desensitization. Nature (Lond) 333: 370–372
Chung FZ, Wang CD, Porter PC. Venter JC & Fraser CM (1988) Site-directed mutagenesis and continuous expression of human β-adrenergic receptors. J Biol Chem 263: 4052–4055
Clark RB (1986) Desensitization of hormonal stimuli coupled to regulation of cAMP levels. Adv Cyclic Nucleotide Protein Phosphorylation Res 20: 151–209
Cotecchia S, Schwinn DA, Randall RR, Lefkowitz RJ, Caron MG & Kobilka BK (1988) Molecular cloning and expression of the cDNA for the hamster α 1,-adrenergic receptor. Proc Natl Acad Sci USA 85: 7159–7163
Dixon RAF, Sigal IF, Rands E, Register RB, Candelore MR, Blake AD & Strader CD (1987) Ligand binding to β-adrenergic receptor involves its rhodopsin-like core. Nature (Lond) 326: 73–77
Dohlman HG, Caron MG, Strader CD, Amlaiky N & Lefkowitz RJ (1988) Identification and sequence of a binding site peptide of the β 2.,-adrenergic receptors. Biochem 27: 1813–1817
Fargin A, Raymond J, Lohse MJ, Kobilka BK, Caron MG & Lefkowitz RJ (1988) The genomic clone which resembles the β-adrenergic receptor sequence and encodes the 5HTIA receptor. Nature (Lond) 335: 358–360
Hausdorff WP, Bouvier M, O’Dowd BF, Irons GP, Caron MG & Lefkowitz RJ (1989) Phosphorylation sites on two domains for the β 2-adrenergic receptor are involved in distinct pathways of receptor desensitization. J Biol Chem 264: 12657–12665
Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG & Lefkowitz RJ (1988) Chimeric β 2-adrenergic receptors: delineation of domains involved in effector coupling in ligand binding specificity. Science 240: 1310–1316
Kunkel MW, Friedman J, Shenolikar S & Clark RB (1989) Cell-free heterologous desensitization of adenylyl cyclase in S49 lymphoma cell membranes mediated by cAMP dependent protein kinase. FASEB J 3: 2067–2074
Lefkowitz RJ & Caron MG (1988) The adrenergic receptors: models for the study of receptors coupled to guanine nucleotide regulatory proteins. J Biol Chem 263: 4993–4996
Liggett SB, Bouvier M, Hausdorff WP, O’Dowd BF, Caron MG & Lefkowitz RJ (1989) Altered patterns of agonist-stimulated cAMP accumulation in cells expressing mutant β2-adrenergic receptors lacking phosphorylation sites. Mol Pharmacol. (in press)
Lohse MJ, Lefkowitz RJ, Caron MG & Benovic JL (1989) Inhibition of β-adrenergic receptor kinase prevents rapid homologous desensitization of the β-adrenergic receptors. Proc Natl Acad Sci USA 86: 3011–3015
O’Dowd BF, Hnatowich M, Regan JW, Leader WM, Caron MG & Lefkowitz RJ (1988) Site directed mutagenesis of the cytoplasmic domains of the human β 2-adrenergic receptor. J Biol Chem 263: 15985–15992
Regan JW, Kobilka TS, Yang Feng DL, Caron MG, Lefkowitz RJ & Kobilka BK (1988) Cloning and expression of a human kidney cDNA for a novel α 2,-adrenergic receptor. Proc Natl Acad Sci USA 85: 6301–6305
Rubinstein RC, Wang SKF & Ross EM (1987) The hydrophobic tryptic core of the β-adrenergic receptor retains Gs, regulatory activity in response to agonists and thiols. J Biol Chem 262: 16655–16662
Sibley DR, Benovic JL, Caron MG & Lefkowitz RJ (1987) Regulation of transmembrane signalling by receptor phosphorylation. Cell 48: 913–922
Strader CD, Dixon RAF, Cheung AH, Candelore MR, Blake AD & Sigal IS (1987a) Mutation that uncoupled the β-adrenergic receptor from Gs, and increased agonist affinity. J Biol Chem 262: 16439–166443
Strader CD, Sigal IS, Register RV, Candelore MR, Rands E & Dixon RAF (1987b) Identification of residues required for ligand binding to the β-adrenergic receptors. Proc Natl Acad Sci USA 84: 4384–4388
Strader CD, Sigal IS, Candelore MR, Rands E, Hill WS & Dixon RAF (1988) Conserved asparatic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function. J Biol Chem 63: 4052–4055
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Caron, M.G. et al. (1989). Catecholamine Receptors: Structure, Function, and Regulation. In: Gehring, U., Helmreich, E.J.M., Schultz, G. (eds) Molecular Mechanisms of Hormone Action. 40. Colloquium der Gesellschaft für Biologische Chemie 6.– 8. April 1989 in Mosbach/Baden, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75022-9_21
Download citation
DOI: https://doi.org/10.1007/978-3-642-75022-9_21
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-75024-3
Online ISBN: 978-3-642-75022-9
eBook Packages: Springer Book Archive