TY - JOUR
T1 - Cyclic adenosine monophosphate accumulation and β-adrenergic binding in unweighted and denervated rat soleus muscle
AU - Kirby, Christopher R.
AU - Woodman, Christopher R.
AU - Woolridge, Dale
AU - Tischler, Marc E.
N1 - Funding Information:
From the Departments of Biochemistry and Physiology. College of Medicine, University of Arizona, Tucson, AZ. Supported by National Aeronautics and Space .4dministration (NASA) Grant No. NAG2-384 (to M.E. T.), NASA Graduate Researcher Program award (to C.R.K.), National Institutes of Health Training Grants No. NS-07309 and No. HL-07249 to the Depanment of Physiology, and Biomedical Research Support Grant No. RR-05675 to the College of Medicine. Address reprint requests to Marc E. Tischler, PhD. Department of Biochemistry, College of Medicine, University ofArizona. Tucson, AZ 85 724. Copyright 0 I992 by W.B . Saunders Company 00260495/92/4107-0021$03.00l0
PY - 1992/7
Y1 - 1992/7
N2 - 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.
AB - 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.
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U2 - 10.1016/0026-0495(92)90323-3
DO - 10.1016/0026-0495(92)90323-3
M3 - Article
C2 - 1320180
AN - SCOPUS:0026753378
SN - 0026-0495
VL - 41
SP - 793
EP - 799
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 7
ER -