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Gene Review

Adrb1  -  adrenergic receptor, beta 1

Mus musculus

Synonyms: Adrb-1, Adrb1r, Beta-1 adrenergic receptor, Beta-1 adrenoceptor, Beta-1 adrenoreceptor, ...
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Disease relevance of Adrb1


High impact information on Adrb1

  • Treatment of these cells with the agonist isoproterenol corresponded to a desensitization of beta AR activity [6].
  • In contrast, beta AR mutants in which the C-terminus was truncated and/or in which two regions that have been proposed as phosphorylation substrates for cAMP-dependent protein kinase were removed showed normal sequestration responses [6].
  • These findings mark CaMKII as a determinant of clinically important heart disease phenotypes, and suggest CaMKII inhibition can be a highly selective approach for targeting adverse myocardial remodeling linked to betaAR signaling [7].
  • Beta-adrenergic receptor (betaAR) stimulation increases cytosolic Ca(2+) to physiologically augment cardiac contraction, whereas excessive betaAR activation causes adverse cardiac remodeling, including myocardial hypertrophy, dilation and dysfunction, in individuals with myocardial infarction [7].
  • Importantly, intermittent pressure overload caused diastolic dysfunction, altered beta-adrenergic receptor (betaAR) function, and vascular rarefaction before the development of cardiac hypertrophy, which were largely normalized by preventing the recruitment of PI3K by betaAR kinase 1 to ligand-activated receptors [8].

Chemical compound and disease context of Adrb1


Biological context of Adrb1

  • The majority of beta 1-AR -/- mice die prenatally, and the penetrance of lethality shows strain dependence [14].
  • In addition to its ability to define beta-AR subtype-specific functions, this genetic approach is also useful in identifying adaptive alterations that serve to maintain critical physiological setpoints such as heart rate, blood pressure, and metabolic rate when cellular signaling mechanisms are perturbed [15].
  • In order to achieve homeostasis in vivo, the cellular signals generated by beta-AR activation are integrated with signals from a number of other distinct receptors and signaling pathways [15].
  • The density of beta-AR was up-regulated to varying degrees in many brain regions of Dbh-/- mice compared to the heterozygotes [16].
  • An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue [17].

Anatomical context of Adrb1


Associations of Adrb1 with chemical compounds


Physical interactions of Adrb1

  • In butyrate-exposed cells, proportions of beta-AR proteins and mRNAs were, respectively, 87 and 94% for beta 1 and 9 and 1% for beta 2-AR. beta 3-ARs were barely detectable in binding assays and accounted for 4.5% of beta-AR transcripts [23].
  • CONCLUSION: The results reveal that simultaneous stimulation of the expression of certain ucp genes and the leptin gene can be achieved, and suggest that adrenergic regulation of the leptin gene and of genes of the ucp family in adipose tissues is the result of complex interactions between the different beta-AR pathways [24].
  • METHODS: Cardiac beta-AR density was measured by [125I]-iodocyanopindolol binding to ventricular membranes [25].
  • The pharmacological evidence and the mRNA analysis are consistent with NE acting through a beta 1-adrenergic receptor positively coupled to adenylate cyclase [26].
  • The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear [27].

Regulatory relationships of Adrb1

  • The ability of individual beta AR subtypes to regulate Ucp expression was examined with combinations of selective beta-adrenergic agonists and antagonists [22].
  • In brown adipose tissue, beta3-adrenoceptor disruption induced a 66% decrease (P < 0.005) in beta1-adrenoceptor mRNA level, whereas leptin mRNA remained unchanged [28].
  • This reciprocal regulation of betaARK1 documents a novel mechanism of ligand-induced betaAR regulation and provides important insights into the potential mechanisms responsible for the effectiveness of beta-blockers, such as carvedilol, in the treatment of heart failure [29].
  • Thus, at the submaximal isoproterenol concentration of 30 nM, the beta 2AR stimulated adenylyl cyclase approximately 50% more than did the beta 1AR [30].
  • We have previously shown that the beta-adrenergic receptor (beta-AR) stimulates activity of the ubiquitous Na-H exchanger (NHE-1) independently of changes in cAMP accumulation and independently of a cholera toxin-sensitive stimulatory GTP-binding protein (Gs) [31].

Other interactions of Adrb1

  • These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes [14].
  • Saturation and competition experiments measuring binding of 125I-labeled (-)-cyanopindolol to adipocyte membranes demonstrated that cell exposure to insulin for 4 days caused a 3.5-fold decrease in the density of the major beta-AR component of the adipocyte, the beta 3-AR, while beta 1-AR sites remained unchanged and beta 2-ARs were undetectable [18].
  • Expression of the betaAR kinase (betaARK1), which phosphorylates and uncouples betaARs, is elevated in human HF; this likely contributes to the abnormal betaAR responsiveness that occurs with beta-agonist administration [32].
  • Furthermore, the in vivo left ventricular contractile response to betaAR stimulation was restored to normal in the hybrid double-transgenic mice [32].
  • To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-) [17].

Analytical, diagnostic and therapeutic context of Adrb1

  • To understand the roles that individual beta-AR subtypes play in these processes, we have used the technique of gene targeting to create homozygous beta 1-AR null mutants (beta 1-AR -/-) in mice [14].
  • RESULTS: Western blots of rat heart nuclear fractions and confocal immunofluorescent analysis of adult rat and mouse ventricular cardiomyocytes displayed the presence of beta 1AR and beta 3AR but, surprisingly, not the beta 2AR on nuclear membranes [19].
  • The densities of alpha(1)-AR, alpha(2)-AR and beta-AR were assayed with [(3)H]prazosin, [(3)H]RX21002 and [(125)I]-iodo-pindolol autoradiography, respectively [16].
  • These findings have caused beta ARs and GRKs to be regarded as potential therapeutic targets, and gene therapy strategies have been used to manipulate the beta AR signaling pathway in myocardium, leading to improved function in the compromised heart [33].
  • In addition, Northern blot analyses indicate that the beta 3AR gene is mainly expressed in mouse brown and white adipose tissues, suggesting that the murine beta 3AR described here is the atypical beta AR involved in the control of energy expenditure in fat tissue [34].


  1. Impaired expression and functional activity of the beta 3- and beta 1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. Collins, S., Daniel, K.W., Rohlfs, E.M., Ramkumar, V., Taylor, I.L., Gettys, T.W. Mol. Endocrinol. (1994) [Pubmed]
  2. Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse. Asai, K., Yang, G.P., Geng, Y.J., Takagi, G., Bishop, S., Ishikawa, Y., Shannon, R.P., Wagner, T.E., Vatner, D.E., Homcy, C.J., Vatner, S.F. J. Clin. Invest. (1999) [Pubmed]
  3. Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice. Engelhardt, S., Hein, L., Wiesmann, F., Lohse, M.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Adrenergic regulation of cardiac myocyte apoptosis. Singh, K., Xiao, L., Remondino, A., Sawyer, D.B., Colucci, W.S. J. Cell. Physiol. (2001) [Pubmed]
  5. Epinephrine promotes pulmonary angiitis: evidence for a beta1-adrenoreceptor-mediated mechanism. Jain, F.A., Zhao, L.H., Selig, M.K., Kradin, R.L. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  6. The carboxyl terminus of the hamster beta-adrenergic receptor expressed in mouse L cells is not required for receptor sequestration. Strader, C.D., Sigal, I.S., Blake, A.D., Cheung, A.H., Register, R.B., Rands, E., Zemcik, B.A., Candelore, M.R., Dixon, R.A. Cell (1987) [Pubmed]
  7. Calmodulin kinase II inhibition protects against structural heart disease. Zhang, R., Khoo, M.S., Wu, Y., Yang, Y., Grueter, C.E., Ni, G., Price, E.E., Thiel, W., Guatimosim, S., Song, L.S., Madu, E.C., Shah, A.N., Vishnivetskaya, T.A., Atkinson, J.B., Gurevich, V.V., Salama, G., Lederer, W.J., Colbran, R.J., Anderson, M.E. Nat. Med. (2005) [Pubmed]
  8. Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction. Perrino, C., Naga Prasad, S.V., Mao, L., Noma, T., Yan, Z., Kim, H.S., Smithies, O., Rockman, H.A. J. Clin. Invest. (2006) [Pubmed]
  9. Evidence for activation by beta2-adrenergic receptors of adenosine 3',5'-monophosphate formation in Ehrlich ascites tumor cells. Onaya, T., Akasu, F., Takazawa, K., Hashizume, K. Endocrinology (1978) [Pubmed]
  10. Influence of beta-adrenoceptor antagonists on hemorrhage-induced cellular immune suppression. Oberbeck, R., van Griensven, M., Nickel, E., Tschernig, T., Wittwer, T., Pape, H.C. Shock (2002) [Pubmed]
  11. Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor. Hinkle, R.T., Hodge, K.M., Cody, D.B., Sheldon, R.J., Kobilka, B.K., Isfort, R.J. Muscle Nerve (2002) [Pubmed]
  12. Beta-adrenergic receptor subtype is an intrinsic property of the receptor gene product. Strader, C.D., Candelore, M.R., Rands, E., Dixon, R.A. Mol. Pharmacol. (1987) [Pubmed]
  13. The metabolic and cardiovascular effects of hyperthyroidism are largely independent of beta-adrenergic stimulation. Bachman, E.S., Hampton, T.G., Dhillon, H., Amende, I., Wang, J., Morgan, J.P., Hollenberg, A.N. Endocrinology (2004) [Pubmed]
  14. Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects. Rohrer, D.K., Desai, K.H., Jasper, J.R., Stevens, M.E., Regula, D.P., Barsh, G.S., Bernstein, D., Kobilka, B.K. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. Rohrer, D.K., Chruscinski, A., Schauble, E.H., Bernstein, D., Kobilka, B.K. J. Biol. Chem. (1999) [Pubmed]
  16. Analysis of brain adrenergic receptors in dopamine-beta-hydroxylase knockout mice. Sanders, J.D., Szot, P., Weinshenker, D., Happe, H.K., Bylund, D.B., Murrin, L.C. Brain Res. (2006) [Pubmed]
  17. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Rockman, H.A., Chien, K.R., Choi, D.J., Iaccarino, G., Hunter, J.J., Ross, J., Lefkowitz, R.J., Koch, W.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  18. Transcriptional down-regulation by insulin of the beta 3-adrenergic receptor expression in 3T3-F442A adipocytes: a mechanism for repressing the cAMP signaling pathway. Fève, B., Elhadri, K., Quignard-Boulangé, A., Pairault, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  19. Functional beta-adrenergic receptor signalling on nuclear membranes in adult rat and mouse ventricular cardiomyocytes. Boivin, B., Lavoie, C., Vaniotis, G., Baragli, A., Villeneuve, L.R., Ethier, N., Trieu, P., Allen, B.G., Hébert, T.E. Cardiovasc. Res. (2006) [Pubmed]
  20. Distribution of adrenergic receptors in the enteric nervous system of the guinea pig, mouse, and rat. Nasser, Y., Ho, W., Sharkey, K.A. J. Comp. Neurol. (2006) [Pubmed]
  21. Expression of beta adrenergic receptors in mouse oocytes and preimplantation embryos. Cikos, S., Veselá, J., Il'ková, G., Rehák, P., Czikková, S., Koppel, J. Mol. Reprod. Dev. (2005) [Pubmed]
  22. Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. Rohlfs, E.M., Daniel, K.W., Premont, R.T., Kozak, L.P., Collins, S. J. Biol. Chem. (1995) [Pubmed]
  23. Transcriptional modulation by n-butyric acid of beta 1-, beta 2-, and beta 3-adrenergic receptor balance in 3T3-F442A adipocytes. Krief, S., Fève, B., Baude, B., Zilberfarb, V., Strosberg, A.D., Pairault, J., Emorine, L.J. J. Biol. Chem. (1994) [Pubmed]
  24. In vivo effects of CGP-12177 on the expression of leptin and uncoupling protein genes in mouse brown and white adipose tissues. Oliver, P., Picó, C., Martínez, N., Bonet, M.L., Palou, A. Int. J. Obes. Relat. Metab. Disord. (2000) [Pubmed]
  25. L-type calcium current and contractility in ventricular myocytes from mice overexpressing the cardiac beta 2-adrenoceptor. Heubach, J.F., Trebess, I., Wettwer, E., Himmel, H.M., Michel, M.C., Kaumann, A.J., Koch, W.J., Harding, S.E., Ravens, U. Cardiovasc. Res. (1999) [Pubmed]
  26. Beta 1-adrenergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via receptors positively coupled to adenylate cyclase. Martínez de la Escalera, G., Choi, A.L., Weiner, R.I. Endocrinology (1992) [Pubmed]
  27. Beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells. Izevbigie, E.B., Bergen, W.G. Proc. Soc. Exp. Biol. Med. (2000) [Pubmed]
  28. Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition. Revelli, J.P., Preitner, F., Samec, S., Muniesa, P., Kuehne, F., Boss, O., Vassalli, J.D., Dulloo, A., Seydoux, J., Giacobino, J.P., Huarte, J., Ody, C. J. Clin. Invest. (1997) [Pubmed]
  29. Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Iaccarino, G., Tomhave, E.D., Lefkowitz, R.J., Koch, W.J. Circulation (1998) [Pubmed]
  30. Beta 1- and beta 2-adrenergic receptors display subtype-selective coupling to Gs. Green, S.A., Holt, B.D., Liggett, S.B. Mol. Pharmacol. (1992) [Pubmed]
  31. Guanine nucleotides regulate beta-adrenergic activation of Na-H exchange independently of receptor coupling to Gs. Barber, D.L., Ganz, M.B. J. Biol. Chem. (1992) [Pubmed]
  32. In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function. Akhter, S.A., Eckhart, A.D., Rockman, H.A., Shotwell, K., Lefkowitz, R.J., Koch, W.J. Circulation (1999) [Pubmed]
  33. Genetic manipulation of myocardial beta-adrenergic receptor activation and desensitization. Hata, J.A., Williams, M.L., Koch, W.J. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  34. Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes. Nahmias, C., Blin, N., Elalouf, J.M., Mattei, M.G., Strosberg, A.D., Emorine, L.J. EMBO J. (1991) [Pubmed]
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