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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/E932    most recent 00175.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Beitzel, F. Articles by Lynch, G. S. Search for Related Content PubMed PubMed Citation Articles by Beitzel, F. Articles by Lynch, G. S.

-Adrenoceptor signaling in regenerating skeletal muscle after -agonist administration

¹Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria; and ²School of Agricultural and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia

Submitted 18 March 2007 ; accepted in final form 4 July 2007

Stimulating the -adrenoceptor (-AR) signaling pathway can enhance the functional repair of skeletal muscle after injury, but long-term use of -AR agonists causes -AR downregulation, which may limit their therapeutic effectiveness. The aim was to examine -AR signaling during early regeneration in rat fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles after bupivacaine injury and test the hypothesis that, during regeneration, -agonist administration does not cause -AR desensitization. Rats received either the -AR agonist fenoterol (1.4 mg·kg^–1·day^–1 ip) or saline for 7 days postinjury. Fenoterol reduced -AR density in regenerating soleus muscles by 42%. Regenerating EDL muscles showed a threefold increase in -AR density, and, again, these values were 43% lower with fenoterol treatment. An amplified adenylate cyclase (AC) response to isoproterenol was observed in cell membrane fragments from EDL and soleus muscles 7 days postinjury. Fenoterol attenuated this increase in regenerating EDL muscles but not soleus muscles. -AR signaling mechanisms were assessed using AC stimulants (NaF, forskolin, and Mn²⁺). Although -agonist treatment reduces -AR density in regenerating muscles, these muscles can produce large cAMP responses relative to healthy (uninjured) muscles. Desensitization of -AR signaling in regenerating muscles is prevented by altered rates of -AR synthesis and/or degradation, changes in G protein populations and coupling efficiency, and altered AC activity. These mechanisms have important therapeutic implications for modulating -AR signaling to enhance muscle repair after injury.

muscle regeneration; -adrenoceptor; muscle function; muscle injury; adenylate cyclase; G protein

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