Cyclic adenosine monophosphate accumulation and β-adrenergic binding in unweighted and denervated rat soleus muscle

Christopher R. Kirby, Christopher R. Woodman, Dale P Woolridge, Marc E Tischler

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases β-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and β-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a β-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular [IM] injection) to a greater degree (P < .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased β-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (Bmax) for [125I]iodo-(-)-pindolol in particulate preparations of unweighted (420 · 10-18 mol/mg muscle) than of control or denervated muscles (285 · 10-18 mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished cAMP accumulation in the presence of theophylline in unweighted muscle (-66% ± 2%) more than in controls (-42% ± 6%, P < .001). These results show that insulin affects cAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

Original languageEnglish (US)
Pages (from-to)793-799
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume41
Issue number7
DOIs
StatePublished - 1992

Fingerprint

Cyclic AMP
Adrenergic Agents
Skeletal Muscle
Muscles
Atrophy
Intramuscular Injections
Denervation
Insulin
Isoproterenol
Muscle Denervation
Pindolol
Insulin Receptor
Carbohydrate Metabolism
Colforsin
Theophylline
Proteolysis
Insulin Resistance

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Cyclic adenosine monophosphate accumulation and β-adrenergic binding in unweighted and denervated rat soleus muscle. / Kirby, Christopher R.; Woodman, Christopher R.; Woolridge, Dale P; Tischler, Marc E.

In: Metabolism: Clinical and Experimental, Vol. 41, No. 7, 1992, p. 793-799.

Research output: Contribution to journalArticle

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