Effects of calcitonin gene-related peptide on cyclic AMP production and relaxation of longitudinal muscle of guinea pig ileum.

The effects of rat calcitonin gene-related peptide (rCGRP) on the content of cyclic nucleotides in the cells of plexus-free longitudinal muscle (LM) of guinea pig ileum relative to smooth muscle relaxation were investigated. In the absence of isobutyl-methyl-xanthine (IBMX), a nonspecific inhibitor of phosphodiesterases, rCGRP significantly increased cyclic 3'5'-adenosine monophosphate (cAMP) content that correlated temporally to the relaxation of the muscle. Cyclic 3'5'-guanosine monophosphate (cGMP) content was not affected by this peptide. IBMX potentiated both the increase in cAMP content and the muscle relaxation induced by rCGRP. rCGRP increased cAMP content in a concentration-dependent manner, with an ED50 value of 7.5 x 10(-9) M. Both the rCGRP-stimulated increase in cAMP content and the rCGRP-induced muscle relaxation were blocked by hCGRP(8-37), a selective antagonist of CGRP receptors. The pA2 value of hCGRP(8-37) for rCGRP-induced inhibition of tension was calculated to be 6.48. These results suggest that CGRP relaxes the LM through its specific receptors and involves the generation of cAMP, but not the generation of cGMP.