A novel receptor for calcitonin gene-related peptide (CGRP) mediates secretion in the rat colon: implications for secretory function in colitis

The receptor responsible for CGRP-induced ion transport and permeability wa s examined in tissues from animals treated 7 days previously with trinitrob enzenesulfonic acid to induce colitis or in controls. CGRP caused a concent ration-dependent increase in short circuit current (I-sc, EC50 21 nM), whic h was abolished in chloride-free buffer but was not blocked by CGRP(8-37) o r tetrodotoxin (TTX). Amylin and adrenomedullin caused only a modest increa se in I-sc. The responses to the linear CGRP(2) receptor agonists [Cys(Et)( 2,7)] hCGRP alpha and [Cys(Acm)(2,7)] hCGRP alpha were considerably smaller than the response to CGRP. These responses were abolished in chloride-free buffer and were TTX sensitive. Atropine, doxantrazole, and indomethacin di d not block the effects of CGRP or the CGRP, agonists. The response to [Cys (Et)(2,7)] hCGRP alpha was not affected by prior desensitization of the CGR P receptor and vice versa, Inflamed rats had a similar secretory response t o CGRP (I-sc, EC50 15 nM) and [Cys(Et)(2,7)] hCGRP alpha as control tissues , while being hyporesponsive to carbachol, CGRP application increased elect rical conductance of inflamed preparations. Taken together, these data sugg est that CGRP may play an important role in the maintenance of host defense in colitis through an apparently novel CGRP receptor located on the coloni c enterocyte.