Receptors for calcitonin gene related peptide (CGRP) in gastrointestinal epithelia

A pharmacological comparison of calcitonin gene related peptide (CGRP) receptors expressed in normal rat colon mucosa and two human adenocarcinoma cell lines has been undertaken. Using voltage-clamp techniques electrogenic ion transport was continuously monitored across either mucosal preparations or confluent epithelial monolayers grown on permeable supports. The data presented at this meeting show that CGRP receptors are preferentially located on the basolateral epithelial surface and that their stimulation by a variety of CGRP analogues results in enhanced CI- secretion mediated via a cyclic AMP dependent mechanism. Responses to rat alpha CGRP in rat descending colon mucosa and in the adenocarcinoma cell line Colony-29 are insensitive to the inhibitory effects of the C-terminal fragment human CGRP(8-37); however, significant inhibition of rat alpha CGRP responses was observed in the parent epithelial cell line HCA-7. This together with the subtle differences seen in agonist orders of potency in the three preparations indicates that different CGRP receptor subtypes exist in the basolateral domains of HCA-7 compared with rat colon and Colony-29 epithelia.