Beta-Adrenoceptor signaling in regenerating skeletal muscle after Beta-agonist administration

Felice Beitze, Martin Sillence, Gordon S. Lynch

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)E932-E940
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume293
Issue number4
DOIs
Publication statusPublished - Oct 2007

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