Catecholamine Receptors: Structure, Function, and Regulation
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.
KeywordsAdenylyl Cyclase Adrenergic Receptor Membrane Span Domain Cytoplasmic Loop Catecholamine Receptor
Unable to display preview. Download preview PDF.
- 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: 7094–7101PubMedGoogle Scholar
- 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: 8879–8882PubMedCrossRefGoogle Scholar
- 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: 9026–9032Google Scholar
- 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) Google Scholar
- 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: 16655–16662Google Scholar
- 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: 16439–166443Google Scholar
- 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: 4052–4055Google Scholar