AJP - Endocrinology and Metabolism, Vol 258, Issue 5 E757-E761, Copyright © 1990 by American Physiological Society
Neural control of glutamine synthetase activity in rat skeletal muscles
B. Feng, M. Konagaya, Y. Konagaya, J. W. Thomas, C. Banner, J. Mill and S. R. Max
Department of Neurology and Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201.
The mechanism of glutamine synthetase induction in rat skeletal muscle
after denervation or limb immobilization was investigated. Adult male rats
were subjected to midthigh section of the sciatic nerve. At 1, 2, and 5 h
and 1, 2, and 7 days after denervation, rats were killed and denervated,
and contralateral control soleus and plantaris muscles were excised,
weighted, homogenized, and assayed for glutamine synthetase. Glutamine
synthetase activity increased approximately twofold 1 h after denervation
in both muscles. By 7 days postdenervation enzyme activity had increased to
three times the control level in plantaris muscle and to four times the
control level in soleus muscle. Increased enzyme activity after nerve
section was associated with increased maximum velocity with no change in
apparent Michaelis constant. Immunotitration with an antiglutamine
synthetase antibody suggested that denervation caused an increase in the
number of glutamine synthetase molecules in muscle. However, Northern-blot
analysis revealed no increase in the steady-state level of glutamine
synthetase mRNA after denervation. A mixing experiment failed to yield
evidence for the presence of a soluble factor involved in regulating the
activity of glutamine synthetase in denervated muscle. A combination of
denervation and dexamethasone injections resulted in additive increases in
glutamine synthetase. Thus the mechanism underlying increased glutamine
synthetase after denervation appears to be posttranscriptional and is
distinct from that of the glucocorticoid-mediated glutamine synthetase
induction previously described by us.
