DOI: 10.1146/annurev.physiol.62.1.237. Functional Consequences of Altering Myocardial Adrenergic Receptor Signaling

Functional Consequences of Altering Myocardial Adrenergic Receptor Signaling

10.1146/annurev.physiol.62.1.237

Crossref journal-article

Annual Reviews

Annual Review of Physiology (22)

Abstract

▪ Abstract From the ability to successfully manipulate the mouse genome has come important transgenic and gene-targeted knockout models that impact many areas of biomedical research. Genetically engineered mouse models geared toward the study of cardiovascular regulation have recently been described and provide powerful tools to study normal and compromised cardiac physiology. The genetic manipulation of the adrenergic receptor (AR) signaling system in the heart, including its regulation by desensitizing kinases, has shed light on the role of this signaling pathway in the regulation of cardiac contractility. One major finding, supported by several mouse models, is that in vivo contractility can be enhanced via alteration of myocardial AR signaling. Thus genetic manipulation of this critical receptor system in the heart represents a novel therapeutic approach for improving function of the failing heart.

Bibliography

Koch, W. J., Lefkowitz, R. J., & Rockman, H. A. (2000). Functional Consequences of Altering Myocardial Adrenergic Receptor Signaling. Annual Review of Physiology, 62(1), 237â260.

Authors 3

W. J. Koch (first)
R. J. Lefkowitz (additional)
H. A. Rockman (additional)

References 96 Referenced 130

Ahlquist RP. 1948. A study of the adrenergic receptors.Am. J. Physiol.153:586– 86 (10.1152/ajplegacy.1948.153.3.586)
Caron MG, Lefkowitz RJ. 1993. Catecholamine receptors: structure, function, and regulation.Recent Prog. Horm. Res.48:277–19 (10.1016/B978-0-12-571148-7.50014-2)
10.1016/0163-7258(93)90030-H
10.1172/JCI118823
{'key': 'b5', 'first-page': '295', 'volume': '35', 'year': '1989', 'journal-title': 'Mol. Pharmacol.'} / Mol. Pharmacol. (1989)
10.1038/36362
Xiao R-P, Avidonin P, Zhou Y-Y, Cheng H, Akhter SA, et al. 1999. Coupling of β2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes.Circ. Res.84:43–52 (10.1161/01.RES.84.1.43)
{'key': 'b8', 'first-page': '267', 'volume': '47', 'year': '1995', 'journal-title': 'Pharmacol. Rev.'} / Pharmacol. Rev. (1995)
{'key': 'b9', 'first-page': 'E663', 'volume': '248', 'year': '1985', 'journal-title': 'Am. J. Physiol.'} / Am. J. Physiol. (1985)
10.1016/S0021-9258(18)82267-0 / J. Biol. Chem. (1993)
Dostal DE, Baker KM. 1998. Angiotensin and endothelin: messengers that couple ventricular stretch to the Na+/H+exchanger and cardiac hypertrophy.Circ. Res.83:870–73 (10.1161/01.RES.83.8.870)
10.1172/JCI111023
10.1074/jbc.273.30.18677
10.1016/S0021-9258(20)80439-6 / J. Biol. Chem. (1993)
Iaccarino G, Rockman HA, Shotwell KF, Tomhave ED, Koch WJ. 1998. Myocardial-targeted overexpression of G protein-coupled receptor kinase-3 in transgenic mice: evidence for in vivo selectivity of GRKs.Am. J. Physiol.275:H1298–306 (10.1152/ajpheart.1998.275.4.H1298)
10.1126/science.1325672
10.1016/S0021-9258(18)53090-8 / J. Biol. Chem. (1993)
Inglese J, Koch WJ, Touhara K, Lefkowitz RJ. 1995. Gβγ interactions with PH domains and Ras-MAP kinase signaling pathways.Trends Biochem. Sci.20:151– 56 (10.1016/S0968-0004(00)88992-6)
10.1074/jbc.270.28.17000
10.1126/science.7761854
10.1161/01.CIR.73.5.913
Bristow MR, Ginsburg R, Minobe W, Cubicciotti R, Sageman WS, et al. 1982. Decreased catecholamine sensitivity and β-adrenergic receptor density in failing human hearts.N. Engl. J. Med.307:205– 11 (10.1056/NEJM198207223070401)
10.1172/JCI116891
Ungerer M, Bohm M, Elce JS, Erdmann E, Lohse ML. 1993. Altered expression of β-adrenergic receptor kinase and β1adrenergic receptors in the failing heart.Circulation87:454–63 (10.1161/01.CIR.87.2.454)
Feldman AM, Cates AE, Veazey WE, Hershberger RE, Bristow MR, et al. 1988. Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.J. Clin. Invest.82:189–97 (10.1172/JCI113569)
Dhalla NS, Dixom IM, Rupp H, Barwinsky J. 1991. Experimental congestive heart failure due to myocardial infarction: sarcolemmal receptors and cation transporters.Basic Res. Cardiol.86:13– 23 (10.1007/978-3-662-30769-4_2)
Ungerer M, Kessebohm K, Kronsbein K, Lohse MJ, Richardt G. 1996. Activation of β-adrenergic receptor kinase during myocardial ischemia.Circ. Res.79:455– 46 (10.1161/01.RES.79.3.455)
Maurice JP, Shah A, Kypson AP, Hata J, White DC, et al. 1999. Molecular βadrenergic signaling abnormalities in failing rabbit hearts after infarction.Am. J. Physiol.In press (10.1152/ajpheart.1999.276.6.H1853)
10.1161/01.CIR.98.17.1783
Iaccarino G, Dolber PC, Lefkowitz RJ, Koch WJ. 1999. β-adrenergic receptor kinase-1 levels in catecholamine-induced myocardial hypertrophy: regulation by β but not α1adrenergic stimulation.Hypertension33:396–401 (10.1161/01.HYP.33.1.396)
10.1074/jbc.272.27.17223
10.1172/JCI119381
Anversa P, Loud AV, Levicky V, Guideri G. 1985. Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy.Am. J. Physiol.248:H876– 82 (10.1152/ajpheart.1985.248.6.H876)
10.1006/jmcc.1997.0628
{'key': 'b35', 'first-page': '74', 'volume': '16', 'year': '1995', 'journal-title': 'Eur. Heart J.'} / Eur. Heart J. (1995)
10.1161/01.CIR.97.9.892
10.1161/01.RES.82.4.407
10.1016/S0021-9258(18)54273-3 / J. Biol. Chem. (1991)
10.1126/science.8160017
10.1172/JCI118587
10.1073/pnas.93.19.10483
10.1038/374272a0
10.1016/0165-6147(93)90048-O
10.1073/pnas.94.1.137
10.1161/01.RES.84.1.43
10.1093/cvr/27.9.1606
{'key': 'b47', 'first-page': 'H1465', 'volume': '271', 'year': '1996', 'journal-title': 'Am. J. Physiol.'} / Am. J. Physiol. (1996)
10.1073/pnas.96.12.7059
10.1161/01.RES.78.4.517
10.1007/s001090050278
10.1073/pnas.93.14.7375
{'key': 'b52', 'first-page': 'H1184', 'volume': '274', 'year': '1998', 'journal-title': 'Am. J. Physiol.'} / Am. J. Physiol. (1998)
10.1073/pnas.91.21.10109
10.1074/jbc.272.34.21253
Harrison SN, Autelitano DJ, Wang BH, Milano C, Du XJ, et al. 1998. Reduced reperfusion-induced Ins(1,4,5)P3 generation and arrhythmias in hearts expressing constitutively active α1B-adrenergic receptors.Circ. Res.83:1232–40 (10.1161/01.RES.83.12.1232)
Lemire I, Allen BG, Rindt H, Hebert TE, 1998. Cardiac-specific overexpression of α1B-AR regulates β-AR activity via molecular crosstalk.J. Mol. Cell. Cardiol.30:1827–39 (10.1006/jmcc.1998.0746)
10.1074/jbc.270.31.18660
10.1126/science.280.5363.574
10.1073/pnas.88.18.8277
10.1073/pnas.94.21.11589
{'key': 'b61', 'first-page': 'H590', 'volume': '272', 'year': '1997', 'journal-title': 'Am. J. Physiol.'} / Am. J. Physiol. (1997)
10.1073/pnas.93.18.9954
10.1073/pnas.93.23.12974
Rossant J. 1996. Mouse mutants and cardiac development: new molecular insights into cardiogenesis.Circ. Res.78:349–53 (10.1161/01.RES.78.3.349)
10.1074/jbc.273.29.18180
10.1074/jbc.271.22.13266
10.1016/S0021-9258(18)98568-6 / J. Biol. Chem. (1991)
10.1074/jbc.270.37.22066
Eckhart AD, Duncan SJ, Akhter SA, Koch WJ. 1998. Specific myocardial interactions in vivo between G proteincoupled receptor kinases and α1B-adrenergic receptors.Circulation98:I-329
Akhter SA, Milano CA, Lefkowitz RJ, Koch WJ. 1996. Specific interactions between adrenergic receptors and receptor kinases in the hearts of hybrid transgenic mice.Circulation94:I-408
10.1074/jbc.271.9.5049
Benovic JL, DeBlasi A, Stone WC, Caron MG, Lefkowitz RJ. 1989. βadrenergic receptor kinase: Primary structure delineates a multigene family.Science246:235–40 (10.1126/science.2552582)
10.1016/S0021-9258(17)42403-3 / J. Biol. Chem. (1994)
10.1124/mol.52.3.456
10.1124/mol.51.6.991
10.1016/S0021-9258(17)42230-7 / J. Biol. Chem. (1994)
Tsimikas S, Koch WJ, Lefkowitz RJ, Rockman HA. 1996. Desensitization of adenosine A1 receptors with cardiac overexpression of the G protein-coupled receptor kinase 6 in transgenic mice.Circulation94:I-408
10.1172/JCI108079
Lorell BH. 1997. Transition from hypertrophy to failure.Circulation96:3824– 27
10.1161/01.HYP.24.6.653
10.1242/dev.124.4.793 / Development (1997)
Manning BS, Koch WJ. 1998. Altering β-adrenergic receptor (AR) kinase activity and βAR signaling in the developing mouse heart.Circulation98:I-329
10.1016/S0092-8674(00)81878-4
10.1016/0092-8674(94)90192-9
10.1073/pnas.95.12.7000
10.1073/pnas.91.26.12706
10.1161/01.CIR.100.6.648
10.1073/pnas.96.11.6400
10.1073/pnas.94.15.8121
10.1172/JCI4059
10.1007/BF03401640
10.1172/JCI119727
10.1074/jbc.274.32.22251
10.1172/JCI2950
10.1172/JCI119157
10.1073/pnas.94.22.12100

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 7:46 a.m.)
Deposited	3 years, 10 months ago (Oct. 16, 2021, 4:56 p.m.)
Indexed	4 weeks, 1 day ago (Aug. 6, 2025, 9:04 a.m.)
Issued	25 years, 6 months ago (March 1, 2000)
Published	25 years, 6 months ago (March 1, 2000)
Published Print	25 years, 6 months ago (March 1, 2000)

Funders 0

None

BibTeX

@article{Koch_2000, title={Functional Consequences of Altering Myocardial Adrenergic Receptor Signaling}, volume={62}, ISSN={1545-1585}, url={http://dx.doi.org/10.1146/annurev.physiol.62.1.237}, DOI={10.1146/annurev.physiol.62.1.237}, number={1}, journal={Annual Review of Physiology}, publisher={Annual Reviews}, author={Koch, W. J. and Lefkowitz, R. J. and Rockman, H. A.}, year={2000}, month=mar, pages={237–260} }

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