HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bengtsson, T. Articles by Cannon, B. Search for Related Content PubMed PubMed Citation Articles by Bengtsson, T. Articles by Cannon, B. Social Bookmarking                      What's this?

Volume 271, Number 52, Issue of December 27, 1996 pp. 33366-33375
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Down-regulation of ₃ Adrenoreceptor Gene Expression in Brown Fat Cells Is Transient and Recovery Is Dependent upon a Short-lived Protein Factor

(Received for publication, May 21, 1996, and in revised form, September 19, 1996)

From The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden and ^§ Institute Cochin de Génétique Moléculaire, Laboratoire d'Immuno-Pharmacologie Moléculaire, CNRS UPR 0415 et Université Paris VII, 22 rue Méchain, F-75014 Paris, France

The regulation of the expression of the ₃ adrenoreceptor gene was examined in the brown adipose tissue of intact mice and in murine brown fat primary cell cultures. Both in vivo and in vitro, high levels of ₃ receptor mRNA were observed. Acute cold exposure of mice resulted in a marked and rapid down-regulation of ₃ gene expression; this down-regulation was, however, transient. Similarly, in brown fat cell cultures, norepinephrine addition led to down-regulation of ₃ gene expression, with a lag phase of 30 min and with an apparent half-life of ₃ mRNA of ~30 min. This down-regulation was stimulated via the ₃ receptors themselves and mediated via cAMP; the apparent affinity of norepinephrine was extremely high (<1 nM). The degradation rate after actinomycin was identical to that after norepinephrine and was not affected by the presence of norepinephrine; thus, the down-regulation was due to cessation of transcription but not to an increased rate of degradation. Notably, inhibition of protein synthesis by cycloheximide also led to down-regulation. The norepinephrine-induced down-regulation was transient; spontaneous recovery occurred after ~18 h and was not due to depletion of adrenergic agent. Recovery did not occur in the presence of cycloheximide. After recovery, the cells showed a functional desensitization of the down-regulation process itself (EC₅₀ now ~10 nM). It is concluded that a down-regulated state cannot explain the functional desensitization of ₃ adrenergic responsiveness observed in brown fat cells isolated from cold-acclimated animals (i.e. physiologically chronically adrenergically stimulated brown fat cells); since the ₃ receptor is not subject to desensitization via phosphorylation processes, no satisfactory explanation for the functional desensitization exists as yet. A model is presented for the down-regulation/recovery process, involving the participation of a phosphorylatable short-lived transcription factor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. S. Dallner, E. Chernogubova, K. A. Brolinson, and T. Bengtsson {beta}3-Adrenergic Receptors Stimulate Glucose Uptake in Brown Adipocytes by Two Mechanisms Independently of Glucose Transporter 4 Translocation Endocrinology, December 1, 2006; 147(12): 5730 - 5739. [Abstract] [Full Text] [PDF]

				E. Chernogubova, D. S. Hutchinson, J. Nedergaard, and T. Bengtsson {alpha}1- and {beta}1-Adrenoceptor Signaling Fully Compensates for {beta}3-Adrenoceptor Deficiency in Brown Adipocyte Norepinephrine-Stimulated Glucose Uptake Endocrinology, May 1, 2005; 146(5): 2271 - 2284. [Abstract] [Full Text] [PDF]

				B. CANNON and J. NEDERGAARD Brown Adipose Tissue: Function and Physiological Significance Physiol Rev, January 1, 2004; 84(1): 277 - 359. [Abstract] [Full Text] [PDF]

				M. Monjo, A. M. Rodriguez, A. Palou, and P. Roca Direct Effects of Testosterone, 17{beta}-Estradiol, and Progesterone on Adrenergic Regulation in Cultured Brown Adipocytes: Potential Mechanism for Gender-Dependent Thermogenesis Endocrinology, November 1, 2003; 144(11): 4923 - 4930. [Abstract] [Full Text] [PDF]

				I. Shabalina, C. Wiklund, T. Bengtsson, A. Jacobsson, B. Cannon, and J. Nedergaard Uncoupling protein-1: involvement in a novel pathway for beta -adrenergic, cAMP-mediated intestinal relaxation Am J Physiol Gastrointest Liver Physiol, November 1, 2002; 283(5): G1107 - G1116. [Abstract] [Full Text] [PDF]

				G. E. Bronnikov, S.-J. Zhang, B. Cannon, and J. Nedergaard A Dual Component Analysis Explains the Distinctive Kinetics of cAMP Accumulation in Brown Adipocytes J. Biol. Chem., December 31, 1999; 274(53): 37770 - 37780. [Abstract] [Full Text] [PDF]

				G. Bronnikov, T. Bengtsson, L. Kramarova, V. Golozoubova, B. Cannon, and J. Nedergaard {beta}1 to {beta}3 Switch in Control of Cyclic Adenosine Monophosphate during Brown Adipocyte Development Explains Distinct {beta}-Adrenoceptor Subtype Mediation of Proliferation and Differentiation Endocrinology, September 1, 1999; 140(9): 4185 - 4197. [Abstract] [Full Text]

				H. M. Guardiola-Diaz, S. Rehnmark, N. Usuda, T. Albrektsen, D. Feltkamp, J.-A. Gustafsson, and S. E. H. Alexson Rat Peroxisome Proliferator-activated Receptors and Brown Adipose Tissue Function during Cold Acclimatization J. Biol. Chem., August 13, 1999; 274(33): 23368 - 23377. [Abstract] [Full Text] [PDF]

				J. Zhao, B. Cannon, and J. Nedergaard Thermogenesis is beta 3- but not beta 1-adrenergically mediated in rat brown fat cells, even after cold acclimation Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1998; 275(6): R2002 - R2011. [Abstract] [Full Text] [PDF]

				J. M. Lindquist and S. Rehnmark Ambient Temperature Regulation of Apoptosis in Brown Adipose Tissue. Erk1/2 PROMOTES NOREPINEPHRINE-DEPENDENT CELL SURVIVAL J. Biol. Chem., November 13, 1998; 273(46): 30147 - 30156. [Abstract] [Full Text] [PDF]

				R. Jockers, T. Issad, V. Zilberfarb, P. de Coppet, S. Marullo, and A. D. Strosberg Desensitization of the {beta}-Adrenergic Response in Human Brown Adipocytes Endocrinology, June 1, 1998; 139(6): 2676 - 2684. [Abstract] [Full Text] [PDF]

				J. M. Lindquist, J. M. Fredriksson, S. Rehnmark, B. Cannon, and J. Nedergaard beta 3- and alpha 1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes J. Biol. Chem., July 21, 2000; 275(30): 22670 - 22677. [Abstract] [Full Text] [PDF]