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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 29, Issue 5


Effects of α-(prazosin and yohimbine) and β-receptors activity on cAMP generation and UCP1 gene expression in brown adipocytes

Hirendra M. Biswas
  • Corresponding author
  • Department of Physiology, Kathmandu Medical College, 184, Baburam Acharya Sadak, Sinamangal, Kathmandu, 44600, Nepal, Phone: +9779860652080 (Nepal), +919874483054 (India)
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Published Online: 2018-04-18 | DOI: https://doi.org/10.1515/jbcpp-2017-0211



Brown adipose tissue (BAT) contains both α- and β-adrenergic receptors. In the literature, the activity of α-adrenoreceptors is less documented, and their functions still remain puzzling. The present investigation has been undertaken to understand α-adrenoreceptors’ activity and their relation between uncoupling protein 1 (UCP1) mRNA expression and cyclic AMP (cAMP) generation in BAT.


BAT precursor cells from young mice were grown in culture. Cells were exposed to norepinephrine (NE) and other agents. RNA was isolated after harvesting the cells, and northern blot was performed. Filters were exposed to film after hybridization with nick-translated complementary DNA probes, and results were evaluated by scanning. Amersham assay kit was used for cAMP measurement.


Treatment of prazosin and yohimbine separately with 1 μM of NE shows stimulation of UCP1 mRNA expression 106% and 154%, respectively, whereas with that of both drugs shows only 76%. cAMP generation occurs 282% with prazosin, 100% with yohimbine, and 382% with both drugs with 1 μM of NE, whereas it is 310%, 40%, and 358%, respectively, with 10 μM of NE.


Stimulation of thermogenesis after treatment of prazosin and NE may be due to the inhibition of phosphodiesterase enzyme and with yohimbine and NE indicates the possibility of inhibition of the inhibitory effect of α2- and stimulation of α1-receptors. Increase of cAMP concentration with yohimbine and both drugs with NE are not correlated to UCP1 mRNA expression. This indicates that the relationship between cAMP elevation and stimulation of thermogenesis is not simple. This study clearly shows the interaction between β- and α-adrenoreceptor activities.

Keywords: α-antagonist; β-agonist; BAT; NE; thermogenesis


  • 1.

    Perkins NM, Rothwell NJ, Stock MJ, Stone TW. Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 1981;289:401–2.CrossrefPubMedGoogle Scholar

  • 2.

    Rehnmark S, Nechad M, Herron D, Cannon B, Nedergaard J. Alpha and beta-adrenergic induction of the expression of the uncoupling protein thermogenin in brown adipocytes differentiated in culture. J Biol Chem 1990;265:16464–71.PubMedGoogle Scholar

  • 3.

    Cannon B, Nedergaard J. The biochemistry of an inefficient tissue: brown adipose tissue. Essays Biochem 1985;20:110–64.PubMedGoogle Scholar

  • 4.

    Nedergaard J, Lindberg O. The brown fat cell. Int Rev Cytol 1982;74:187–286.CrossrefPubMedGoogle Scholar

  • 5.

    Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physiol Rev 1984;64:1–64.PubMedCrossrefGoogle Scholar

  • 6.

    Nedergaard J, Cannon B. The uncoupling protein thermogenin and mitochondrial thermogenesis. In: Ernster L, editor. Comprehensive biochemistry: molecular mechanism in bioenergetics, vol. 23. Amsterdam: Elsevier, 1992:385–420.Google Scholar

  • 7.

    Schulz TJ, Tseng Y-H. Brown adipose tissue: development, metabolism and beyond. Biochem J 2013;453:167–78.Web of ScienceCrossrefPubMedGoogle Scholar

  • 8.

    Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277–359.CrossrefPubMedGoogle Scholar

  • 9.

    Mohell N, Svartengren J, Cannon B. Identification of (3H) prazosin binding sites in crude membranes and isolated cells of brown adipose tissue as alpha-1 adrenergic receptors. Eur J Pharmacol 1983;92:15–25.PubMedCrossrefGoogle Scholar

  • 10.

    Raasmaja A, Mohell N, Nedergaard J. Increased alpha-1 adrenergic receptor density in brown adipose tissue of cold-acclimated rats and hamsters. Eur J Pharmacol 1985;106:489–98.Google Scholar

  • 11.

    Zhao J, Cannon B, Nedergaard J. Alpha-1 adrenergic stimulation potentiates the thermogenic action of beta-3 adrenoreceptor-generated cAMP in brown fat cells. J Biol Chem 1997;272:32847–56.PubMedCrossrefGoogle Scholar

  • 12.

    Nedergaard J, Biswas H, Bronikov G, Jacobsson A, Kikuchi-Utsumi K, Kikuchi-Utsumi M, et al. Alpha-1 adrenergic receptors in brown adipose tissue during cold acclimation and hibernation: density and functional significance. In: Geise F, Hulbert AJ, Nicol SC, editors. Adaptation to cold. Tenth International Hibernation Symposium. Armidale: University of New England Press, 1996:281–91.Google Scholar

  • 13.

    Schimmel RJ, McCarthy L, McMahon KK. Alpha-1 adrenergic stimulation of hamster brown adipocyte respiration. Am J Physiol 1983;244:C362–8.CrossrefPubMedGoogle Scholar

  • 14.

    Nechad M, Kuusela P, Carnehein C, Bjorntorp P, Nedergaard J, Cannon B. Development of brown fat cells in monolayer culture, I. Morphological and biochemical distinction from white fat cells in culture. Exp Cell Res 1983;149:105–18.PubMedGoogle Scholar

  • 15.

    Jacobsson A, Stadler U, Glotzer MA, Kozak LP. Mitochondrial uncoupling protein from mouse brown fat: molecular cloning, genetic mapping and mRNA expression. J Biol Chem 1985;260:1625–4.Google Scholar

  • 16.

    Jacobsson A, Nedergaard J, Cannon B. Alpha and beta adrenergic control of thermogenin mRNA expression in brown adipose tissue. Biosci Rep 1986;6:621–31.CrossrefPubMedGoogle Scholar

  • 17.

    Kozak LP. Interacting genes control glycerol-3-phosphate dehydrogenase expression in developing cerebellum of the mouse. Genetics 1985;110:123–43.PubMedGoogle Scholar

  • 18.

    Bronnikov GE, Zhang S-J, Cannon B, Nedergaard J. A dual component analysis explains the distinctive kinetics of cAMP accumulation in brown adipocytes. J Biol Chem 1999;274:37770–80.CrossrefPubMedGoogle Scholar

  • 19.

    McIntyre J, Hull D, Nedergaard J, Cannon B. Thermoregulation. In: Gluckman PD, Heyman MA, editors. Perinatal and pediatric pathophysiology, a clinical perspective. London: Edward Arnold, 1993:357–68.Google Scholar

  • 20.

    Wilcke M, Nedergaard J. Alpha-1 and beta-adrenergic regulation of intracellular Ca2+ levels in brown adipocytes. Biochem Biophys Res Commun 1989;163:292–300.CrossrefPubMedGoogle Scholar

  • 21.

    McMohan KK, Scimmel RJ. Apparent absence alpha-2 adrenergic receptors from hamster brown adipocytes. Life Sci 1982;30:1185–92.PubMedCrossrefGoogle Scholar

  • 22.

    Bourova L, Pesanova Z, Novotny J, Bengtsson T, Svoboda P. Differentiation of cultured brown adipocytes is associated with a selective increase in the short variant of G(s) alpha protein. Evidence for higher functional activity of G(s) alpha S. Mol Cell Endocrinol Metab 2000;167:23–31.CrossrefGoogle Scholar

  • 23.

    Wu YY, Goldfien A, Roberts JM. Alpha adrenergic stimulation reduces cyclic adenosine 3′, 5′-monophosphate generation in rabbit myometrium by two mechanisms. Biol Reprod 1988;39:58–65.CrossrefPubMedGoogle Scholar

  • 24.

    Lafontan M, Berlan M, Galitzky J, Montastruc JL. Alpha-2 adrenoreceptors in lipolysis: alpha-2 antagonists and lipid-mobilizing strategies. Am J Clin Nutr 1992;55:219s–27s.CrossrefGoogle Scholar

  • 25.

    Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 2009;9:203–9.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 26.

    Madden CJ, Tupone D, Cano G, Morrison SF. Alpha-2 adrenergic receptor-mediated inhibition of thermogenesis. J Neurosci 2013;33:2017–28.CrossrefWeb of SciencePubMedGoogle Scholar

  • 27.

    Galitzky J, Verrnovel M, Lafontan M, Montastrue P, Berlan M. Thermogenic and lipolytic effect of yohimbine in the dog. Br J Pharmacol 1991;104:514–8.PubMedCrossrefGoogle Scholar

  • 28.

    Biswas HM. Effect of phosphodiesterase inhibitors on UCP 1 gene expression in brown adipocytes. Adapt Med 2015;7:78–82.CrossrefGoogle Scholar

  • 29.

    Biswas HM. Effect of adrenocorticotropic hormone on UCP1 gene expression in brown adipocytes. J Basic Clin Physiol Pharmacol 2017;28:267–74.PubMedGoogle Scholar

  • 30.

    Nedergaard J, Ricquier D, Kozak LP. Uncoupling proteins: current status and therapeutic prospects. EMBO Rep 2005;6:917–21.CrossrefPubMedGoogle Scholar

  • 31.

    Schafer A, Fraccarollo D, Pfortsch S, Flierl U, Vogt C, Pfrang J, et al. Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus. Br J Pharmacol 2008;153:886–93.Web of SciencePubMedGoogle Scholar

  • 32.

    Handa P, Tateya S, Rizzo NO, Cheng AM, Morgan-Stevenson V, Han CY, et al. Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue inflammation during high fat feeding. Arterioscler Thromb Vasc Biol 2011;31:2827–35.CrossrefWeb of SciencePubMedGoogle Scholar

About the article

Received: 2017-05-23

Accepted: 2018-01-15

Published Online: 2018-04-18

Published in Print: 2018-09-25

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Swedish Natural Science Research Council.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 29, Issue 5, Pages 545–552, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2017-0211.

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