ANTAGONISM OF THE EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE AND OF CAPSAICIN ON THE GUINEA-PIG ISOLATED ILEUM BY HUMAN ALPHA-CALCITONIN GENE-RELATED PEPTIDE(8-37)

The possible mediating role of calcitonin gene-related peptide (CGRP) in the effects of capsaicin in the guinea-pig ileum has been investigated by means of the CGRP antagonist hCGRP(8-37). Submaximal longitudinal muscle relaxation of the histamine-precontracted ileum evoked by rat CGRP (3 nM) or capsaicin (1-mu-M) was reversed by hCGRP(8-37) (1.5-mu-M), while that due to adrenaline or neurotensin was not affected. Inhibition of spontaneous circular muscle movements by capsaicin (100 nM) was also reversed by hCGRP(8-37). The CGRP antagonist had no effect on electrical stimulation-evoked ileal contractions or on the longitudinal or circular muscle tone. It is concluded that (a) hCGRP(8-37) is a specific CGRP antagonist in the ileum, apparently devoid of intrinsic activity or any effect not related to CGRP; (b) the inhibitory actions of capsaicin on the longitudinal and circular muscles of the ileum are mediated, at least in part, by CGRP.