Effect of denervation of the phrenic nerve on the action of calcitonin gene-related peptide in rat diaphragm.

The effect of denervation on Calcitonin gene-related peptide (CGRP)-induced enhancement of the twitch contraction of skeletal muscle was studied. In rat diaphragm denervated 2 weeks previously, the basal twitch contraction induced by transmural stimulation was about twice that in control muscle, and the basal adenylate cyclase activity and cyclic AMP (cAMP) contents of the tissue were increased. This denervation did not affect the dose-dependent beta -adrenergic stimulation of twitch contraction, but abolished the CGRP-induced enhancement of twitch contraction. The latter phenomenon seems to be caused in part by decrease in CGRP-induced accumulation of cAMP over the basal level, because of increase in the basal cAMP level after denervation. The involvement of another inhibitory second messenger system coupled with CGRP receptors is discussed.