Calcitonin gene-related peptide receptors in human gastrointestinal epithelia

Br J Pharmacol. 1994 Dec;113(4):1243-8. doi: 10.1111/j.1476-5381.1994.tb17131.x.


1. The secretory responses to calcitonin gene-related peptide (CGRP) receptor agonists have been characterized in two human adenocarcinoma cell lines, namely HCA-7 and Colony-29 (Col-29) epithelia. These cells form polarized epithelial layers when grown on permeable supports and allow changes in electrogenic ion transport in response to agonists to be monitored continuously. 2. alpha-CGRP (rat and human sequences), rat beta-CGRP and human [Tyr0]CGRP applied to the basolateral surface were found to be full agonists, causing prolonged increases in short-circuit current. Concentration-response curves exhibited EC50 values of 0.6-1.5 nM in HCA-7 cells. The same agonists were less effective in Col-29 epithelia, the EC50 values ranging from 1 to 10 nM in these cells. [Cys(ACM)2,7]CGRP was effective in both cell lines and was more potent in HCA-7 cells. 3. CGRP receptors were preferentially located on the basolateral surface in both cell types. Addition of r alpha-CGRP to the apical domain produced significantly smaller secretory responses (8.1% in HCA-7 and 29.2% in Col-29) compared with those produced following basolateral application (100%). 4. In both cell lines r alpha-CGRP-elevated short-circuit current was inhibited by the loop diuretic piretanide (200 microM) and by somatostatin (100 nM). Pretreating epithelia with the cyclo-oxygenase inhibitor, piroxicam (5 microM) had no significant effect upon CGRP responses in either cell line. 5. Rat alpha-CGRP (0.2 nM) responses in HCA-7 epithelia were inhibited by the C-terminal fragment CGRP(8-37) (1 microM). Pretreatment of Col-29 cells with CGRP(8-37) did not, however, alter the size or profile of responses to r alpha-CGRP (1 nM).6. We conclude that high-affinity CGRP receptors exist on the basolateral surface of both cell lines,however they differ in their sensitivity to CGRP(8-37) and agonist orders of potency. Thus different CGRP receptor subtypes appear to predominate in these two epithelial cell types.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / analogs & derivatives
  • Calcitonin Gene-Related Peptide / pharmacology
  • Cell Line
  • Diuretics / pharmacology
  • Electrophysiology
  • Epithelial Cells
  • Epithelium / anatomy & histology
  • Epithelium / metabolism
  • Gastric Mucosa / anatomy & histology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Humans
  • Intestinal Mucosa / anatomy & histology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Piroxicam / pharmacology
  • Rats
  • Receptors, Calcitonin Gene-Related Peptide / agonists
  • Receptors, Calcitonin Gene-Related Peptide / metabolism*
  • Somatostatin / pharmacology
  • Sulfonamides / pharmacology
  • Tumor Cells, Cultured


  • Diuretics
  • Receptors, Calcitonin Gene-Related Peptide
  • Sulfonamides
  • Piroxicam
  • Somatostatin
  • piretanide
  • Calcitonin Gene-Related Peptide