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Gs Protein-Coupled Receptors in Human Heart

  • Chapter
The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 148))

Abstract

Endogenous amines, such as the neurotransmitter noradrenaline or humoral adrenaline, 5-hydroxytryptamine (5-HT) and histamine, enhance the rate and force of the heart beat. These amines act as agonists at specific membrane receptors that are usually coupled to the Gs protein which, in turn, usually uses adenylyl cyclase as an effector. Activation of some of these receptors can be beneficial or harmful to heart function. Some interesting properties of these cardiac receptors will be discussed, particularly their function in human heart. A vast array of cardiac tissues and cells from animals have been used as models of human heart function. Surprisingly, extrapolations and inferences about receptor-mediated modulation of human heart function from results obtained from animal cardiac tissues and cells can be misleading, resulting in the need for direct experimentation on human heart tissues and cells. The aim of this article is to concentrate on quantitative aspects of the function of coexisting Gs protein-coupled receptors in human heart to ascertain their relative importance. The value of choice of relevant animal models is critically stressed. The function of individual receptors will be compared first, followed by some indirect evidence for cross-talk among Gs-coupled receptors.

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References

  • Altschuld R, Starling RC, Hamlin RL, Billman GE, Hensley J, Castillo L, Fertel RH, Hohl CM, Robitaille P-ML, Jones L, Xiao RP, Lakatta EG (1995) Response of failing canine and human heart cells to β 2-adrenergic stimulation. Circulation 92: 1612–1618

    Article  PubMed  CAS  Google Scholar 

  • Arch JRS (1997) β 3-adrenoceptors and other putative β-adrenoceptors. Pharmacol Res Commun 9:141–148

    CAS  Google Scholar 

  • Arch JRS, Kaumann (1993) β 3- and atypical β-adrenoceptors. Med Res Rev 14:663–729

    Article  Google Scholar 

  • Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann A J, Levy FO (2000) 5-HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. Naunyn-Schmiedeberg’s Arch Pharmacol (in press)

    Google Scholar 

  • Bateman DN (1986) The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam. Eur J Clin Pharmacol 30:205–208

    Article  PubMed  CAS  Google Scholar 

  • Bearer CF, Knapp RD, Kaumann AJ, Swartz TL, Birnbaumer L (1980) Iodohydroxy-benzylpindolol: preparation, localization of its iodine to the indole ring, and characterization as a partial agonist. Mol Pharmacol 17:328–338

    PubMed  CAS  Google Scholar 

  • Begin-Heick (1995) β 3-adrenoceptor activation of adenylyl cyclase in mouse white adipocytes: modulation by GTP and effect of obesity. J Cell Biochem 58:464–473

    Article  Google Scholar 

  • Berkowitz DE, Nardone NA, Smiley RM, Price DTY, Kreutter DK, Fremeau RT, Schwinn R. (1995) Distribution of β 3-adrenoceptor mRNA in human tissues. Eur J Pharmacol 289:223–228

    Article  PubMed  CAS  Google Scholar 

  • Berman DM, Gilman AG (1998) Mammalian RGS proteins: barbarians at the gate. J Biol Chem 273:1269–1272

    Article  PubMed  CAS  Google Scholar 

  • Berman DM, Kosaza T, Gilman AG (1996) The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J Biol Chem 271:27209–27212

    Article  PubMed  CAS  Google Scholar 

  • Billman GE, Castillo LC, Hensley J, Hohl CM, Altschuld RA (1997) β 2-adrenergic receptor antagonists protect against ventricular fibrillation. In vivo and in vitro evidence for enhanced sensitivity to β 2-adrenergic stimulation in animals susceptible to sudden death. Circulation 96:1914–1922

    Article  PubMed  CAS  Google Scholar 

  • Black JW (1989) Drugs from emasculated hormones: the principle of synaptic antagonism. Science 245:486–493

    Article  PubMed  CAS  Google Scholar 

  • Black JW, Duncan WAM, Durant CJ, Ganellin CR, Parsons EM (1972) Definition and antagonism of histamine H2-receptors. Nature 236:385–390

    Article  PubMed  CAS  Google Scholar 

  • Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune U, Langlois M, Fischmeister R (1997) Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium. FEBS Lett 412(3):465–474

    Article  PubMed  CAS  Google Scholar 

  • Bockaert J, Claeysen S, Dumuis A (1998) Molecular biology, function and pharmacological role of 5-HT4 receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 358:R 10

    Google Scholar 

  • Bond RA, Clarke DE (1988) Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α- and β-subtypes. Br J Pharmacol 95:723–734

    Article  PubMed  CAS  Google Scholar 

  • Bond RA, Lefkowitz RJ (1996) The third beta is not a charm. J Clin Invest 98:241

    Article  PubMed  CAS  Google Scholar 

  • Bond RA, Leff P, Johnson TD, Milano CA, Rockman HA, McMinn TR, Apparsun-daram S, Hyek MF, Kenakin TP, Allen LF, Lefkowitz RJ (1995) Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β 2-adrenoceptor. Nature 374:272–276

    Article  PubMed  CAS  Google Scholar 

  • Borea PA, Amerini S, Masini I, Cerbai E, Ledda F, Mantelli L, Varani K, Mugelli A (1992) β 1- and β 2-adrenoceptors in sheep cardiac ventricular muscle. J Mol Cell Cardiol 24:753–764

    Article  PubMed  CAS  Google Scholar 

  • Bristow MR, Ginsburg R, Minobe W, Cubiciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB (1982) Decreased catecholamine sensitivity and β-adrenergic receptor density in failing human hearts. N Engl J Med 307:205–211

    Article  PubMed  CAS  Google Scholar 

  • Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Melove R, Shah P, Jamieson S, Stinson EB (1986) β 1 and β 2-adrenergic receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β 1-receptor down-regulation in heart failure. Circ Res 59:297–309

    Article  PubMed  CAS  Google Scholar 

  • Bristow MR, Hershberger RE, Port JD, Rasmussen R (1989) β 1 and β 2-adrenergic receptor-mediated adenylate cyclase in non-failing and failing human ventricular myocardium. Mol Pharmacol 35:295–303

    PubMed  CAS  Google Scholar 

  • Brown LA, Harding SE (1992) The effect of pertussis toxin on β-adrenoceptor responses in isolated cardiac myocytes from noradrenaline-treated guinea pigs and patients with cardiac failure. Br J Pharmacol 106:115–122

    Article  PubMed  CAS  Google Scholar 

  • Burrel KM, Molenaar P, Dawson PJ, Kaumann A J (2000) Contractile and arrhythmic effects of endothelin receptor agonists in human heart in vitro: blockade by SB 209670. J Pharmacol Exp Ther 292:440–459

    Google Scholar 

  • Buxton BF, Jones CR, Molenaar P, Summers RJ (1987) Characterization and autoradiographic localization of β-adrenoceptor subtypes in human cardiac tissues. Br J Pharmacol 92:299–310

    Article  PubMed  CAS  Google Scholar 

  • Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, Molinoff PB, Ruffolo RR Jr, Trendelenburg U (1994) IV International Union of Pharmacology Nomenclature of Adrenoceptors. Pharmacol Rev 46:121–136

    PubMed  CAS  Google Scholar 

  • Carlsson E, Åblad B, Brandström A, Carlsson B (1972) Differential blockade of the chronotropic effects of various adrenergic stimuli in cat heart. Life Sci 11:953–958

    Article  CAS  Google Scholar 

  • Chaudry A, MacKenzie RG, Georgic LM, Granneman JG (1994) Differential interaction of β 1 and β 3-adrenoceptor with Gi in rat adipocytes. Cell Signalling 6:457–465

    Article  Google Scholar 

  • Chruscinski AJ, Rohrer DK, Schäuble E, Desai KH, Bernstein D, Kobilka BK (1999) Targeted disruption of the β 2 adrenergic gene. J Biol Chem 274:16694–16700

    Article  PubMed  CAS  Google Scholar 

  • Claeysen S, Seben M, Journot L, Bockaert J, Dumuis A (1996) Cloning, expression and pharmacology of the mouse 5-HT4L receptor. FEBS Lett 398:19–25

    Article  PubMed  CAS  Google Scholar 

  • Claeysen S, Faye P, Seben M, Lemaire S, Bockaert J, Dumuis A (1997) Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase. Neuroreport 8:3189–3196

    Article  PubMed  CAS  Google Scholar 

  • Cohen RA (1985) Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter 5-hydroxytryptamine. J Clin Invest 75:286–292

    Article  PubMed  CAS  Google Scholar 

  • Del Monte F, Kaumann AJ, Poole-Wilson PA, Wynne DG, Pepper J, Harding SE. (1993) Coexistence of functioning β 1 and β 2-adrenoceptors in single myocytes from human ventricle. Circulation 88:854–863

    Article  PubMed  Google Scholar 

  • Du X-J, Autelitano DJ, Dilley RJ, Wang B, Dart AM, Woodcock EA (2000) β 2-adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis. Circulation 101:71–77

    Article  PubMed  CAS  Google Scholar 

  • Dumuis A, Bouhelal R, Seben M, Cory R, Bockaert J (1988) A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol Pharmacol 34:880–887

    PubMed  CAS  Google Scholar 

  • Dumuis A, Seben M, Bockaert J (1989) The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurones. Naunyn-Schmiedeberg’s Arch Pharmacol 340:403–410

    Article  CAS  Google Scholar 

  • Elnatan J, Molenaar P, Rosenfeldt FL, Summers RJ (1994) Autoradiographic localization and quantitation of β 1- and β 2-adrenoceptors in human atrioventricular conducting system: a comparison of patients with idiopathic dilated cardiomyopathy and ischemic heart disease. J Mol Cell Cardiol 26:313–323

    Article  PubMed  CAS  Google Scholar 

  • Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko SE, Strosberg AD (1989) Molecular characterization of the human β 3-adrenoceptor. Science 245:1118–1121

    Article  PubMed  CAS  Google Scholar 

  • Engelhardt S, Hein L, Wiesmann F, Lohse MJ (1999) Progressive hypertrophy and heart failure in β 1-radrenergic receptor transgenic mice. Proc Natl Acad Sci USA 96:7059–7064

    Article  PubMed  CAS  Google Scholar 

  • Feldman AM, Gates AE, Veazey WB, Hershberger RE, Bristow MR, Baughman KL, Baumgartner WA, Van Dop C (1988) Increase of the 40,000 mol wt pertussis toxin substrate (G protein) in the failing human heart. J Clin Invest 82:189–197

    Article  PubMed  CAS  Google Scholar 

  • Ferro A, Kaumann AJ, Brown MJ (1995) β-adrenoceptor subtypes in human coronary artery: desensitization of β 2-adrenergic stimulation in vitro. J Cardiovasc Pharmacol 25:134–141

    Article  PubMed  CAS  Google Scholar 

  • Freestone NS, Heubach J, Wettwer E, Ravens U, Brown D, Kaumann AJ (1999) Putative β 4-adrenoceptors are more effective than β 1-adrenoceptors in mediating arrhythmic Ca2+ transients in mouse ventricular myocytes. Naunyn-Schmiedeberg’s Arch Pharmacol 360:445–456

    Article  CAS  Google Scholar 

  • Gauthier C, Tavernier G, Charpentier F, Langin D, Le Marec H (1996) Functional β 3-adrenoceptor in the human heart. J Clin Invest 98:556–562

    Article  PubMed  CAS  Google Scholar 

  • Gauthier C, Leblais V, Kobzig L, Trochu J-N, Khandoudi N, Bril A, Balligand J-L, Le Marec H (1998) The negative inotropic effect of β 3-adrenoceptor stimulation is mediated by activation of anitric oxide synthase in human ventricle. J Clin Invest 102:1377–1384

    Article  PubMed  CAS  Google Scholar 

  • Gerald C, Adham N, Kao H-T, Olson MA, Laz TM, Schechter LE, Bard JA, Vaysee PJJ, Hartig PR, Branchek TA, Weinshank RL (1995) The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 14:2806–2815

    PubMed  CAS  Google Scholar 

  • Germack R, Starzec AB, Vassy R, Perret G (1997) β-Adrenoceptor subtype expression and function in rat white adipocytes. Br J Pharmacol 120:201–210

    Article  PubMed  CAS  Google Scholar 

  • Gille R, Lemoine H, Ehle B, Kaumann AJ (1985) The affinity of (–)-propranolol for β 1 and β 2-adrenoceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (–)-noradrenaline and (–)-adrenaline. Naunyn-Schmiedeberg’s Arch Pharmacol 331:60–70

    Article  CAS  Google Scholar 

  • Green SA, Holt BD, Liggett SB (1992) β 1- and β 2-receptors display subtype-selective coupling to Gs. Mol Pharmacol 41:889–893

    PubMed  CAS  Google Scholar 

  • Hall JA, Kaumann AJ, Brown MJ (1990) Selective β 1-adrenoceptor blockade enhances positive inotropic effects of endogenous catecholamines through β 2-adrenoceptors in human atrium. Circ Res 66:1610–1623

    Article  PubMed  CAS  Google Scholar 

  • Harding SE (1997) Lack of evidence for β 3-adrenoceptor modulation of contractile force in human ventricular myocytes. Circulation 95:1–53

    Article  Google Scholar 

  • Hartig PR, Hoyer D, Humphrey PPA, Martin GR (1996) Alignment of receptor nomenclature with the human genome: classification of 5-HT1B and 5-HT1D receptor subtypes. Trends Pharmacol Sci 17:103–105

    Article  PubMed  CAS  Google Scholar 

  • Hennekens CH, Albert CM, Godfriend SL, Gaziano JM, Buring SE (1996) Adjunctive therapy of acute myocardial infarction — evidence from clinical trials. N Engl J Med 335:1660–1667

    Article  PubMed  CAS  Google Scholar 

  • Hill SJ, Ganellin CR Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunak W, Levi R, Haas HL. (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 49:253–278

    PubMed  CAS  Google Scholar 

  • Hollander W, Michelson AL, Wilkins RW. (1957) Serotonin and antiserotonins. I. Their circulatory, respiratory and renal effects in man. Circulation 16:246–255

    Article  PubMed  CAS  Google Scholar 

  • Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994) VII International Union of Pharmacology Classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46:157–203

    PubMed  CAS  Google Scholar 

  • Huang C, Hepler JR, Gilman AG, Mumby SM (1997) Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells. Proc Natl Acad Sci USA 94:6159–6163

    Article  PubMed  CAS  Google Scholar 

  • Inman W, Kunota K (1992) Tachycardia during cisapride treatment. Br med J 305:1019

    Article  CAS  Google Scholar 

  • Iskos D, Dutton J, Scheinman MM, Lurie KG (1998) Usefulness of pindolol in neurocardiogenic syncope. Am J Cardiol 82:1121–1124

    Article  PubMed  CAS  Google Scholar 

  • Jahnel U, Rupp J, Ertl R, Nawrath H (1992) Positive inotropic responses to 5-HT in human atrial but not in ventricular muscle. Naunyn-Schmiedeberg’s Arch Pharmacol 346:482–485

    CAS  Google Scholar 

  • Jahnel U, Nawrath H, Rupp J, Ochi R (1993) L-type calcium channel activity in human atrial myocytes as influenced by 5-HT. Naunyn-Schmiedeberg’s Arch Pharmacol 348:396–402

    CAS  Google Scholar 

  • Jakob SM, Becker H, Hanrath P, Schumacher C, Eschenhagen T, Schmitz W, Scholz H, Steinfath M (1996) Effects of metoprolol on myocardial beta-adrenoceptors and Gi alpha-proteins in patients with congestive heart failure. Eur J Clin Pharmacol 51(2):127–132

    Article  PubMed  Google Scholar 

  • Kaumann AJ (1970) Adrenergic receptors in heart muscle: relations among factors influencing the sensitivity of the cat papillary muscle to catecholamines. J Pharmacol Exp Ther 173:383–398

    PubMed  CAS  Google Scholar 

  • Kaumann AJ (1973) Adrenergic receptors in cardiac muscle. Two different mechanisms of β-blockers as partial agonists. Int. Union of Biochemistry, Symposium Nr 52, Acta Physiol Latamer 23:235–236

    Google Scholar 

  • Kaumann AJ (1983) Cardiac β-adrenoceptors — experimental viewpoints. Z Kardiol 72:63–82

    PubMed  CAS  Google Scholar 

  • Kaumann AJ (1989) Is there a third heart β-adrenoceptor? Trends Pharmacol Sci 10:316–320

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ (1990) Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 342:619–622

    CAS  Google Scholar 

  • Kaumann AJ (1991a) 5-HT4-like receptors in mammalian atria. J Neural Transm [Suppl] 34:195–201

    CAS  Google Scholar 

  • Kaumann AJ (1991b) Some aspects of heart beta adrenoceptor function. Cardiovasc Drugs Ther 5:549–560

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ (1993) Blockade of human atrial 5-HT4 receptors by GR 113808. Br J Pharmacol 110:1172–1174

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ (1994) Do human atrial 5-HT4 receptors mediate arrhythmias? Trends Pharmacol Sci 15:451–455

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ (1996) (–)-CGP-12177-induced increase of human atrial contraction through a putative third β-adrenoceptor. Br J Pharmacol 117:93–98

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ (1997) Four β-adrenoceptor subtypes in mammalian heart. Trends Pharmacol Sci 18:70–76

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Blinks JR (1980) β-adrenoceptor blocking agents as partial agonists in isolated heart muscle: dissociation of stimulation and blockade. Naunyn-Schmiedeberg’s Arch Pharmacol 311:205–218

    Article  CAS  Google Scholar 

  • Kaumann AJ, Lemoine H (1987) β 2-adrenoceptor-mediated positive inotropic effects of adrenaline in human ventricular myocardium. Quantitative discrepancies between binding and adenylate cyclase stimulation. Naunyn-Schmiedeberg’s Arch Pharmacol 335:403–411

    Article  CAS  Google Scholar 

  • Kaumann AJ, Lobnig BM (1986) Mode of action of (–)-pindolol on feline and human myocardium. Br J Pharmacol 89:207–218

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Lynham JA (1997) (–)-CGP-12177 stimulates cyclic AMP-dependent protein kinase in rat atria through an atypical β-adrenoceptor. Br J Pharmacol 120:1187–1189

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Molenaar P (1996) Differences between the third cardiac β-adrenoeeptor and the colonic β 3-adrenoceptor in the rat. Br J Pharmacol 118:2085–2098

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Molenaar P (1997) Modulation of human cardiac function through 4 β-adrenoceptor populations. Naunyn-Schmiedeberg’s Arch Pharmacol 355:667–681

    Article  CAS  Google Scholar 

  • Kaumann AJ, Sanders L (1993) Both β 1- and β 2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human atrium. Naunyn-Schmiedeberg’s Arch Pharmacol 348:536–540

    CAS  Google Scholar 

  • Kaumann AJ, Sanders L (1994) 5-Hydroxytryptamine causes rate-dependent arrhythmias through 5-HT4 receptors in human atrium: facilitation by chronic β-adrenoceptor blockade. Naunyn-Schmiedeberg’s Arch Pharmacol 349:331–337

    CAS  Google Scholar 

  • Kaumann AJ, Morris TH, Birnbaumer L (1979) A comparison of the influence of N-isopropyl and N-tert butyl substituents on the affinity of ligands for sinoatrial β-adrenoceptors in rat atria and β-adrenoceptor-coupled adenylyl cyclase in kitten ventricle. Naunyn-Schmiedeberg’s Arch Pharmacol 307:1–8

    Article  CAS  Google Scholar 

  • Kaumann AJ, Lemoine H, Schwederski-Menke U, Ehle B (1989a) Relations between β-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium. Acute desensitization and comparison with feline myocardium. Naunyn-Schmiedeberg’s Arch Pharmacol 339:99–112

    CAS  Google Scholar 

  • Kaumann AJ, Murray KJ, Brown AM, Sanders L, Brown MJ (1989b) A receptor for 5-HT in human atrium. Br J Pharmacol 98:664P

    Google Scholar 

  • Kaumann AJ, Hall JA, Murray KJ, Wells FC, Brown MJ (1989c) A comparison of the effects of adrenaline and noradrenaline on human heart: the role of adenylate cyclase and contractile force. Eur Heart J 10 [Suppl B]:29–37

    PubMed  CAS  Google Scholar 

  • Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1990) A 5-hydrox-ytryptamine receptor in human atrium. Br J Pharmacol 100:879–885

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1991a) A 5-HT4-like receptor in human right atrium. Naunyn-Schmiedeberg’s Arch Pharmacol 344:150–159

    Article  CAS  Google Scholar 

  • Kaumann AJ, Brown AM, Raval P (1991b) Putative 5-HT4-like receptors in piglet left atrium. Br J Pharmacol 101:98P

    Google Scholar 

  • Kaumann AJ, Frenken M, Posival H, Brown AM (1994a) Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1Dβ receptors. Circulation 90:1141–1153

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Gaster LM, King FD, Brown AM (1994b) Blockade of human atrial 5-HT4 receptors by SB-207710, a selective and high affinity 5-HT4 receptor antagonist. Naunyn-Schmiedeberg’s Arch Pharmacol 349:546–548

    Article  CAS  Google Scholar 

  • Kaumann AJ, Lynham JA, Sanders L, Brown AM, Molenaar P (1995a) Contribution of differential efficacy to the pharmacology of human β 1- and β 2-adrenoceptors. Pharmacol Comm 6:215–222

    CAS  Google Scholar 

  • Kaumann AJ, Lynham JA, Brown AM (1995b) Labelling with [125]-SB-207710 of a small 5-HT4 receptor population in piglet right atrium: functional relevance. Br J Pharmacol 115:933–936

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Sanders L, Lynham JA, Bartel S, Kuschel M, Karczweski P, Krause EG (1996a) β 2-adrenoceptor activation by zinterol causes protein phosphorylation, contractile effects and relaxant effects through a cAMP pathway in human atrium. Mol Cell Biochem 163/164:113–123

    Article  PubMed  Google Scholar 

  • Kaumann AJ, Lynham JA, Brown AM (1996b) Comparison of the densities of 5-HT4 receptors, β 1- and β 2-adrenoceptors in human atrium: functional implications. Naunyn-Schmiedeberg’s Arch Pharmacol 353: 592–595

    CAS  Google Scholar 

  • Kaumann AJ, Lynham JA, Sarsero D, Molenaar P (1997) The atypical cardiac cardios-timulant β-adrenoceptor is distinct from β 3-adrenoceptor and is coupled to a cyclic, AMP-dependent pathway in rat and human myocardium. Br J Pharmacol 120:102 P

    Article  Google Scholar 

  • Kaumann AJ, Preitner F, Sarsero D, Molenaar P, Revelli J-P, Giacobino JP (1998) (–)-CGP-12177 causes cardiostimulation and binds to cardiac putative β 4-adrenoceptors in both wild-type and β 3-adrenoceptor knockout mice. Mol Pharmacol 53:670–675

    PubMed  CAS  Google Scholar 

  • Kaumann AJ, Bartel S, Molenaar P, Sanders L, Burrell K, Vetter D, Hempel P, Kar-czewski P, Krause EG (1999) Activation of β 2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I and C protein in ventricular myocardium from patients with terminal heart failure. Circulation 99:65–72

    Article  PubMed  CAS  Google Scholar 

  • Kaumann AJ, Engelhardt S, Molenaar P, Lohse M (2000) (–)-CGP 12177-evoked cardiostimulation is abolished in double β 1/β 2-adrenoceptor (AR) knockout mice. Proc Aust Soc Clin Exp Pharmacol Toxicol 7:70

    Google Scholar 

  • Kenakin T (1995) Agonist receptor efficacy II: agonist trafficking of receptor signals. Trends Pharmacol Sci 16:232–238

    Article  PubMed  CAS  Google Scholar 

  • Kenakin T (1997) Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry. Trends Pharmacol Sci 18:456–464

    PubMed  CAS  Google Scholar 

  • Kent RS, De Lean A, Lefkowitz RJ (1980) A quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modelling of ligand binding data. Mol Pharmacol 17:14–23

    PubMed  CAS  Google Scholar 

  • Koch WJ, Milano CA, Lefkowitz RJ (1966) Transgenic manipulation of myocardial G protein-coupled receptors and receptor kinases. Circ Res 78:511–516

    Article  Google Scholar 

  • Krief S, Lönnqvist F, Raimbault S, Baude B, van Spronson A, Arner P, Strosberg AD, Riquier D, Emorine LJ (1993) Tissue distribution of β 3-adrenoceptor mRNA in man. J Clin Invest 91:344–349

    Article  PubMed  CAS  Google Scholar 

  • Le Messurier DH, Schwartz CJ, Whelan R (1959) Cardiovascular effects of intravenous 5-hydroxytryptamine in man. Br J Pharmacol 14:246–250

    Google Scholar 

  • Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel (1998) Clinical effects of β-adrenergic blockade in chronic heart failure. A meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 98:1184–1191

    Article  PubMed  CAS  Google Scholar 

  • Lemoine H, Kaumann AJ (1982) A novel analysis of concentration-dependence of partial agonism. Naunyn-Schmiedeberg’s Arch Pharmacol 320:130–144

    Article  CAS  Google Scholar 

  • Lemoine H, Kaumann AJ (1991) Regional differences of β 1- and β 2-adrenoceptor-mediated functions in feline heart. A β 2-adrenoceptor-mediated positive inotropic effect possibly unrelated to cyclic AMP. Naunyn-Schmiedeberg’s Arch Pharmacol 344:56–69

    CAS  Google Scholar 

  • Lemoine H, Schönell H, Kaumann AJ (1988) Contribution of β 1- and β 2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (–)-atenolol. Br J Pharmacol 95:55–66

    Article  PubMed  CAS  Google Scholar 

  • Levy FO, Zhu X, Kaumann AJ, Birnbaumer L (1993) Efficacy of β 1-adrenergic receptors is lower than that of β 2-adrenergic receptors. Proc Natl Acad Sci USA 90: 10798–10802

    Article  PubMed  CAS  Google Scholar 

  • Liggett SB, Wagoner LE, Craft LL, Hornung RW, Hoit BD, Mcintosh TC, Walsh RA (1998) The He 164 β 2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 102:1534–1539

    Article  PubMed  CAS  Google Scholar 

  • Londos C, Salomon Y, Lin MC, Harwood JP, Schramm M, Wolff J, Rodbell M (1974) 5-guanylylimidodiphosphate, a potent activator of adenylate cyclase system in eukaryotic cells. Proc Nat Acad Sci 71:3087–3090

    Article  PubMed  CAS  Google Scholar 

  • Lorraine J, Grosset A, O’Connor E (1992) 5-HT4 receptors, present in piglet atria and sensitive to SDZ 205–557, are absent in papillary muscle. Eur J Pharmacol 229: 105–108

    Article  Google Scholar 

  • Lowe MD, Grace AA, Vandenberg JI, Kaumann AJ (1998) Action potential shortening through the putative β 4-adrenoceptor in ferret ventricle: comparison with β 1 and β 2-adrenoceptor-mediated effects. Br J Pharmacol 124:1341–1344

    Article  PubMed  CAS  Google Scholar 

  • Lundin L, Nordheim I, Landelius J, Oberg K, Theodorsson-Nordheim E (1988) Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities. Circulation 77:264–269

    Article  PubMed  CAS  Google Scholar 

  • Malinowska B, Schlicker E (1996) Mediation of the positive chronotropic effect of CGP-12177 and cyanopindolol in the pithed rat by atypical β-adrenoeeptors, different from β 3-adrenoceptors. Br J Pharmacol 117:943–949

    Article  PubMed  CAS  Google Scholar 

  • Man’Int Veld AJ, Schalekamp MADH (1981) Pindolol acts as a beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications. Br Med J 282:929–931

    Article  Google Scholar 

  • Marano M, Kaumann AJ (1976) On the statistics of drug-receptor constants for partial agonists. J Pharmacol Exp Hier 198:518–526

    CAS  Google Scholar 

  • Mason DA, Moore JD, Green SA, Liggett SB (1999) A gain-of-function polymorphism in a G-protein coupling domain of the human β 1-adrenergic receptor. J Biol Chem 274:12670–12674

    Article  PubMed  CAS  Google Scholar 

  • Medhurst A, Kaumann AJ (1993) Characterisation of the 5-HT4 receptor mediating tachycardia in isolated piglet right atrium. Br J Pharmacol 110:1023–1030

    Article  PubMed  CAS  Google Scholar 

  • Mewes T, Dutz S, Ravens U, Jakob KH (1993) Activation of calcium currents in myocytes by empty β-adrenoceptors. Circulation 88:2916–2922

    Article  PubMed  CAS  Google Scholar 

  • Milano CA, Allen LF, Rockman HA, Dolber PC, McMinn TR, Chien KR, Johnson TD, Bond RA, Lefkowitz RJ (1994) Enhanced myocardial function in transgenic mice overexpressing the β 2-adrenergic receptor. Science 264:582–586

    Article  PubMed  CAS  Google Scholar 

  • Mohr B, Bom AH, Kaumann AJ, Thämer V (1987) Reflex inhibition of the efferent renal sympathetic activity by 5-hydroxytryptamine and nicotine elicited by different epicardial receptors. Pflügers Arch 409:145–151

    Article  PubMed  CAS  Google Scholar 

  • Molenaar P, Smolich JJ, Russell FD, McMartin LR, Summers RJ (1990a) Differential regulation of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system after (–)-isoproterenol infusion. J Pharmacol Exp Ther 255:393–400

    PubMed  CAS  Google Scholar 

  • Molenaar P, Canale E, Summers RJ (1990b) Densitometrie analysis of β 1-and β 2-adrenoceptors in guinea-pig atrioventricular conducting system. J Mol Cell Cardiol 22:483–495

    Article  PubMed  CAS  Google Scholar 

  • Molenaar P, Sarsero D, Kaumann AJ (1997a) Proposal for the interaction of non-conventional partial agonists and catecholamines with the ‘putative β 4-adrenoceptor’ in mammalian heart. Clin Exp Pharmacol Physiol 24:647–656

    Article  PubMed  CAS  Google Scholar 

  • Molenaar P Sarsero D, Arch JRS, Kelly J, Henson SM, Kaumann AJ (1997b) Effects of (–)-RO363 at human atrial β-adrenoceptor subtypes, the human cloned β 3-adrenoceptor and rodent intestinal β 3-adrenoceptors. Br J Pharmacol 120:165–176

    Article  PubMed  CAS  Google Scholar 

  • Molenaar P, Sarsero D, Lynham JA, Kaumann AJ (1998) The putative β 4-adrenoceptor activates the cyclic AMP pathway in human heart: inhibition of positive inotropic responses by adenosine and carbachol. Naunyn-Schmiedeberg’s Arch Pharmacol 358:R629

    Google Scholar 

  • Müller FU, Boheler KR, Eschenhagen T, Schmitz W, Scholz H (1993) Isoprenaline stimulates gene transcription of the inhibitory G-protein Giα 2 in rat heart. Circ Res 72:696–700

    Article  PubMed  Google Scholar 

  • Nanoff C, Freissmuth M, Schütz W(1987) The role of a low β 1-adrenoceptor selectivity of [3H]-CGP-12177 for resolving subtype-selectivity of competitive ligands. Naunyn-Schmiedeberg’s Arch Pharmacol 336:519–525

    CAS  Google Scholar 

  • Nantel F, Bonin H, Emorine LJ, Zilberfarb V, Strosberg AD, Bouvier M, Marullo S (1993) The human β 3-adrenoceptor is resistant to short-term agonist-promoted desensitization. Mol Pharmacol 43:548–555

    PubMed  CAS  Google Scholar 

  • Neumann J, Schmitz W, Scholz H, Meyerink LV, Döring V, Kalma P (1988) Increase in myocardial Gi-proteins in heart failure. Lancet 11:936–937

    Article  Google Scholar 

  • Olssen S, Edwards IR (1992) Tachycardia during cisapride treatment. Br med J 305:748–749

    Article  Google Scholar 

  • Oostendorp J, Kaumann AJ (2000) Pertussis toxin suppresses carbachol-evoked car-diodepression but does not modify cardiostimulation mediated through β 1- and putative β 4-adrenoceptors in mouse left atria: no evidence for β 2- and β 3-adrenoceptor function. Naunyn-Schmiedeberg’s Arch Pharmacol 361:134–145

    Article  CAS  Google Scholar 

  • Ormerod OJM, McGregor CGA, Stone DL, Wisbey C, Petch MC (1984) Arrhythmias after coronary bypass surgery. Br Heart J 51:618–621

    Article  PubMed  CAS  Google Scholar 

  • Ouadid H, Seguin J, Dumuis A, Bockaert J, Nargeot J (1992) Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptor. Mol Pharmacol 41:346–351

    PubMed  CAS  Google Scholar 

  • Pak MD, Fishman PH (1996) Anomalous behavior of CGP-12177 A on β 1-adrenergic receptors. J Receptor Signal Transduction Research 16 (1 and 2):1–23

    Article  Google Scholar 

  • Parker SG, Taylor EM, Hamburger SA, Vimal M, Kaumann AJ (1995) Blockade of human and porcine myocardial 5-HT4 receptors by SB 203186. Naunyn-Schmiedeberg’s Arch Pharmacol 335:28–35

    Google Scholar 

  • Ping P, Gelzer-Bell R, Roth DA, Kiel D, Insel PA, Hammond HK (1995) Reduced β-adrenergic receptor kinase activity in porcine heart. J Clin Invest 95:1271–1280

    Article  PubMed  CAS  Google Scholar 

  • Pino R, Cerbai E, Calamai G, Alajmo F, Borgioli A, Braconi L, Cassai M, Montesi GF, Mugelli A (1998) Effect of 5-HT4 receptor stimulation on the pacemaker current If in human isolated atrial myocytes. Cardiovasc Res 40:516–522

    Article  PubMed  CAS  Google Scholar 

  • Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ (1992) Role of βγsubunits of G proteins in targeting the β-adrenergic receptor kinase to membrane-bound receptors. Science 257:1264–1267

    Article  PubMed  CAS  Google Scholar 

  • Pritchard BNC, Tomlinson B, Waiden RJ, Bhattacharjee P (1983) The β-adrenergic blockade withdrawal phenomenon. J Cardiovasc Pharmacol 5 [Suppl 1]:56–62

    Article  Google Scholar 

  • Rahme MM, Cotter B, Leistad E, Wadha MK, Mohabir R, Ford APDW, Eglen RM, Feld GK (1999) Electrophysiological and antiarrhythmic effects of the atrial selective 5-HT4 receptor antagonist RS-100302 in experimental atrial flutter and fibrillation. Circulation 100:2010–2017

    Article  PubMed  CAS  Google Scholar 

  • Reithmann C, Gierschik P, Sidiropoulos D, Werdan K, Jakobs KH (1989) Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein α-subunits. Eur J Pharmacol 172:211–221

    Article  PubMed  CAS  Google Scholar 

  • Rockman HA, Chien KE, Choi D-J, Iaccarino G, Hunter JJ, Ross Jr J, Lefkowitz RJ, Koch WJ (1998) Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci USA 95:7000–7005

    Article  PubMed  CAS  Google Scholar 

  • Rodbell M, Krans HMJ, Pohl SL, Birnbaumer L (1971) The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. IV. Effects of guanyl nucleotides on binding of 125I-glucagon. J Biol Chem 246:1872–1876

    PubMed  CAS  Google Scholar 

  • Rohrer DK, Chruscinski A, Schauble EH, Bernstein D, Kobilka BK (1999) Cardiovascular and metabolic alterations in mice lacking both β 1- and β 2-adrenergic receptors. J Biol Chem 274:16701–16708

    Article  PubMed  CAS  Google Scholar 

  • Sanders L, Kaumann AJ (1992) A 5-HT4-like receptor in human left atrium. Naunyn-Schmiedeberg’s Arch Pharmacol 345:382–386

    CAS  Google Scholar 

  • Sanders L, Lynham JA, Bond B, del Monte F, Harding SE, Kaumann AJ (1995) Sensitization of human atrial 5-HT4 receptors by chronic β blocker treatment. Circulation 92:2526–2639

    Article  PubMed  CAS  Google Scholar 

  • Sanders L, Lynham JA, Kaumann AJ (1996) Chronic β 1-adrenoceptor blockade sensitises the H1 and H2 receptor systems in human atrium. Naunyn-Schmiedeberg’s Arch Pharmacol 353:661–670

    Article  CAS  Google Scholar 

  • Sarsero D, Molenaar P, Kaumann AJ (1998a) Validity of (–)-[3H]-CGP-12177 as a radioligand for the “putative β 4-adrenoceptor” in rat atrium. Br J Pharmacol 123: 371–380

    Article  PubMed  CAS  Google Scholar 

  • Sarsero D, Molenaar P, Kaumann AJ (1998b) The “putative β 4-adrenoceptor” mediates positive inotropic responses and hastens relaxation through a cAMP pathway in human heart. Aust NZ J Med 28:147

    Google Scholar 

  • Sarsero D, Molenaar P, Kaumann AJ (1998c) (–)-[3H]-CGP-12177 radiolabels β 1-, β 2- and putative β 4-adrenoceptors in human atrium and ventricle. Naunyn-Schmiedeberg’s Arch Pharmacol 358:R 629

    Google Scholar 

  • Sarsero D, Molenaar P, Kaumann AJ, Freestone NS (1999) Putative β 4-adrenoceptors mediate increases in contractile force and cell Ca2+: comparison with atrial responses and relationship to (–)-[3H]-CGP 12177 binding. Br J Pharmacol 128:1445–1460

    Article  PubMed  CAS  Google Scholar 

  • Sawada M, Ichinose M, Ito I, Maeno T, Mcadoo DJ (1984) Effects of 5-hydroxytryptamine on membrane potential, contractility, accumulation of cyclic AMP, and Ca2+ movements in anterior aorta and ventricle of Aplysia. J Neurophysiol 51:361–374

    PubMed  CAS  Google Scholar 

  • Sennitt MV, Kaumann AJ, Molenaar P, Beeley LJ, Young PW, Kelly K, Chapman H, Henson SM, Berge JM, Dean DK, Kotecha NR, Morgan HKA, Rami HK, Ward RW, Thompson M, Wilson S, Smith SA, Cawthorne MA, Stock MJ, Arch JRS (1998) The contribution of classical (β 1/2-) and atypical β-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel β 3-adrenoceptor agonists of different selectivities. J Pharmacol Exp Ther 285:1084–1095

    PubMed  CAS  Google Scholar 

  • Skeberdis VA, Jurevicius J, Fischmeister R (1997) β 2-Adrenergic activation of L-type Ca++ current in cardiac myocytes. J Pharmacol Exp Ther 282:452–461

    Google Scholar 

  • Skeberdis VA, Jurevicius J, Fischmeister R (1999) β 3-Adrenergic regulation of L-type Ca2+ current in human atrial myocytes. Abstract to the 43rd Annual Meeting of the Biophysical Society, February 13–17, Baltimore, Maryland, USA

    Google Scholar 

  • Sole MJ, Shum A, VanLoon GR (1979) Serotonin: metabolism in the normal and failing heart. Circ Res 45:629–634

    Article  PubMed  CAS  Google Scholar 

  • Soriano JB, Hoes AW, Meems L, Grobee DE (1997) Increased survival with β blockers: importance of ancillary properties. Progress in Cardiovascular Diseases 39:445–456

    Article  PubMed  CAS  Google Scholar 

  • Staehelin M, Simons P, Jaeggi K, Wigger H (1983) CGP-12177. A hydrophilic β-adrenergic receptor radioligand reveals high affinity binding of agonists to intact cells. J Biol Chem 258:3496–3502

    PubMed  CAS  Google Scholar 

  • Stephenson RP (1956) A modification of receptor theory. Br J Pharmacol 11:379–393

    CAS  Google Scholar 

  • Summers RJ, Molenaar P (1995) Autoradiography of β 1- and β 2-adrenoceptors. In: Methods in Molecular Biology 41: Signal transductions protocols. Kendall DA, Hill SJ, eds, Humana Press Inc Totowa NJ, pp 25–39

    Google Scholar 

  • Turki J, Lorenz JN, Green SA, Donnelly ET, Jacinto M, Liggett SB (1996) Myocardial signalling defects and impaired cardiac function of a human β 2-adrenergic receptor polymorphism expressed in transgenic mice. Proc Natl Acad Sci USA 93:10483–10488

    Article  PubMed  CAS  Google Scholar 

  • Ungerer M, Böhm M, Elce JS, Erdmann E, Lohse MJ (1993) Altered expression of β-adrenergic receptor kinase and β 1-adrenergic receptors in failing human heart. Circulation 87:454–463

    Article  PubMed  CAS  Google Scholar 

  • Van den Wyngaert I, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W, Bender E (1997) Cloning and expression of a human serotonin 5-HT4 receptor cDNA. J Neurochem 69:1810–1819

    Article  PubMed  Google Scholar 

  • Villalon CM, Den Boer MO, Heiligers JPC, Saxena PR (1991) Further characterization, by use of tryptamine and benzamide derivatives, of the putative 5-HT4 receptor mediating tachycardia in the pig. Br J Pharmacol 102:107–112

    Article  PubMed  CAS  Google Scholar 

  • Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, Gilbert EM, Johnson MR, Gross FG, Hjalmarson A (1993) Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet 342:1441–1446

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Kaumann AJ, Brown MJ (1996) (–)-Timolol is a more potent antagonist of the positive inotropic effects of (–)-adrenaline than those of (–)-noradrenaline in human atrium. Br J Clin Pharmacol 42:217–223

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Plumpton C, Brown MJ (1999) Selective β 1-adrenoceptor blockade enhances the activity of the stimulatory G-protein in human atrial myocardium. Br J Pharmacol 128:135–141

    Article  PubMed  CAS  Google Scholar 

  • Waud DR (1969) On the measurement of the affinity of partial agonists for receptors. J Pharmacol Exp Ther 170:117–122

    PubMed  CAS  Google Scholar 

  • Witte K, Schnecko A, Olbrich HG, Lemmer B (1995) Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters. Eur J Pharmacol 290:1–10

    Article  PubMed  CAS  Google Scholar 

  • Witte K, Schnecko A, Hauth D, Wirzius S, Lemmer B (1998) Effects of chronic application of propranolol on β-adrenergic signal transduction in heart ventricles from myopathic BIO TO2 and control hamsters. Br J Pharmacol 125:1033–1041

    Article  PubMed  CAS  Google Scholar 

  • Xiao RP, Ji X, Lakatta EG (1994) Functional coupling of the β 2-adrenoceptor to a pertussis toxin-sensitive G protein in cardiac myocytes. Mol Pharmacol 47:322–329

    Google Scholar 

  • Xiao R-P, Avdonin P, Zhou Y-Y, Cheng H, Akhter SA, Eschenhagen T, Lefkowitz RJ, Koch WJ, Lakatta EG (1999) Coupling of β 2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes. Circ Res 84:43–52

    Article  PubMed  CAS  Google Scholar 

  • Zerkowski H-R, Broede A, Kunde K, Hillemann S, Schäfer E, Vogelsang M, Michel MC, Brodde O-E (1993) Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium. Naunyn-Schmiedeberg’s Arch Pharmacol 346:347–352

    Google Scholar 

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  1. Department of Receptor Biochemistry, Glaxo Wellcome Research and Development, 5 Moore Drive, Research Triangle Park, 27709, NC, USA

    Terry Kenakin Ph.D. (Principal Research Scientist) (Principal Research Scientist)

  2. Department of Pharmacology, The University of Melbourne, 3010, Parkville, VIC, Australia

    James A. Angus Ph.D. FAA (Head) (Head)

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Kaumann, A.J. (2000). Gs Protein-Coupled Receptors in Human Heart. In: Kenakin, T., Angus, J.A. (eds) The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems. Handbook of Experimental Pharmacology, vol 148. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57081-0_4

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