STUDIES ON THE MECHANISM OF THE CONTRACTILE ACTION OF RAT CALCITONIN-GENE-RELATED PEPTIDE AND OF CAPSAICIN ON THE GUINEA-PIG ILEUM - EFFECTOF HCGRP (8-37) AND CGRP TACHYPHYLAXIS

Both the neuropeptide calcitonin gene-related peptide (CGRP) and the s ensory stimulant drug capsaicin exert excitatory as well as inhibitory actions in the guinea-pig ileum. It has been known that their excitat ory effects are due to activation of myenteric neurons. In the present study it has been established that a fairly high concentration (3 muM ) of the CGRP antagonist human alpha CGRP (8-37) [hCGRP (8-37)], which has been known to reverse the inhibitory effects of rCGRP, failed to inhibit longitudinal contractions of ileal longitudinal muscle-myenter ic plexus strips due to rat (r) CGRP. Instead, a slight enhancement of the contractions was observed, probably due to the inhibition of the relaxant effect. Tachyphylaxis to rCGRP was able to markedly reduce th e contractile action of rCGRP but did not influence contractions due t o capsaicin (1 muM). It is concluded that myenteric neuronal excitatio n due to rCGRP involves receptors not sensitive to hCGRP (8-37). Moreo ver, neuronal excitation by capsaicin does not seem to involve a CGRP- like mediator.