Volume 113, Issue 4 p. 1243-1248
Free Access

Calcitonin gene-related peptide receptors in human gastrointestinal epithelia

H.M. Cox

Corresponding Author

H.M. Cox

Department of Pharmacology, The Royal College of Surgeons of England, 35-43, Lincoln's Inn Fields, London WC2A 3PN

Department of Pharmacology, The Royal College of Surgeons of England, 35-43, Lincoln's Inn Fields, London WC2A 3PNSearch for more papers by this author
I.R. Tough

I.R. Tough

Department of Pharmacology, The Royal College of Surgeons of England, 35-43, Lincoln's Inn Fields, London WC2A 3PN

Search for more papers by this author
First published: December 1994
Citations: 25

Abstract

  • 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

    α-CGRP (rat and human sequences), rat β-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 rα-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 rα-CGRP-elevated short-circuit current was inhibited by the loop diuretic piretanide (200μm) and by somatostatin (100 nm). Pretreating epithelia with the cyclo-oxygenase inhibitor, piroxicam (5μm) had no significant effect upon CGRP responses in either cell line.

  • 5

    Rat α-CGRP (0.2 nm) responses in HCA-7 epithelia were inhibited by the C-terminal fragment CGRP(8–37) (1 μm). Pretreatment of Col-29 cells with CGRP(8–37) did not, however, alter the size or profile of responses to rα-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.