Cyclic AMP and Cyclic GMP in Skeletal Muscles
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Cross innervation studies of fast and slow muscles have shown that motoneurons regulate the speed of contraction, enzyme activities of aerobic and anaerobic glycolysis, calcium uptake of sarcoplasmic reticulum and synthesis of myosin protein. However, mechanism of these regulations is not fully elucidated. Cyclic 3', 5'-AMP (cAMP) is known to regulate the activation of phosphorylase 6 kinase kinase which regulates glycogenolysis and also has many biological activities.<BR>In this study, cAMP and cyclic GMP (cGMP) were measured by the competitive protein binding assays (Gilman, Murad, and Illiano) on white and red muscles.<BR>1) In the state of relaxation, white (fast) muscles contained lower levels of cAMP than those of red (slow) muscles. Pyruvate kinase activity could be regarded as an indicator of differentiation of muscle fibers. Administration of d-tubocurarine caused a significant increase of cAMP in fast muscles.<BR>2) However, adenyl cyclase activities of gastrocnemius and soleus muscles were not different, assayed in the presence of 10 mM NaF.<BR>3) Denervation made by excision of sciatic nerve caused an increase of cAMP/wet weight in gastrocnemius muscles of the rats after 2 weeks.<BR>4) Adenyl cyclase activity of the gastrocnemius muscle from a patient with Duchenne type dystrophy, of which electron microscopic finding revealed only dilated sarcoplasmic reticulum, was lower than controls. Change of cyclase system in the early stage of the dystrophy can be a trigger of the pathologic process.<BR>5) Cyclic GMP was measured after purification on alumina and Dowex 1×8 columns. The concentrations of cGMP of white and red muscles of rabbits were compared with those of cAMP and they showed different levels each other. This suggests that there might exist separate regulatory controls of cAMP and cGMP in skeletal muscle.<BR>Muscle contraction seemed to cause a decrease in cGMP level without change of cAMP.<BR>These results suggest that cAMP may play a role in the so-called trophic influence of nerve on muscle differentiation.
- Japan Society of Clinical Chemistryの論文
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