The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin.

1. The content of calcitonin-gene-related-peptide-like immunoreactivity (CGRP-LI) in various rat muscles was measured. Starvation for 24 h did not affect the content of CGRP-LI in these muscles, except for a decreased level in the starved-rat diaphragm. Higher contents of CGRP-LI were observed in well-vascularized muscles. 2. Capsaicin (at 1, 10 and 100 microM) inhibited insulin-stimulated rates of glycogen synthesis in isolated stripped incubated soleus muscle preparations by a mechanism independent of catecholamine release, since the effects of capsaicin were not altered by the beta-adrenoreceptor antagonist DL-propranolol. 3. Resiniferatoxin (10 nM), which is a potent capsaicin agonist, also significantly inhibited the insulin-stimulated rate of glycogen synthesis. Furthermore, the concentration of resiniferatoxin required to inhibit glycogen synthesis was 100 times less than the concentration of capsaicin needed for the same effect. 4. Capsaicin (10 microM) decreased the content of CGRP-LI in isolated stripped incubated soleus muscle preparations by about 40%. 5. Neonatal treatment of rats with capsaicin, which causes de-afferentation of some sensory nerves such, we hypothesize, that CGRP can no longer be released to counteract the effects of insulin in vivo, caused increased rates of glycogen synthesis and increased glycogen content in stripped soleus muscle preparations in vitro when muscles were isolated from the adult rats. 6. These findings support the hypothesis that capsaicin and resiniferatoxin elicit an excitatory response on sensory nerves in skeletal muscle in vitro to cause the efferent release of CGRP. Consequently, CGRP is delivered to skeletal muscle fibres to inhibit insulin-stimulated glycogen synthesis. The role of CGRP in recovery of blood glucose levels during hypoglycaemia is discussed.