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 was examined in tissues from animals treated 7 days previously with trinitrobenzenesulfonic acid to induce colitis or in controls. CGRP caused a concentration-dependent increase in short circuit current (I(sc), EC(50) 21 nM), which was abolished in chloride-free buffer but was not blocked by CGRP(8-37) or tetrodotoxin (TTX). Amylin and adrenomedullin caused only a modest increase in I(sc). The responses to the linear CGRP(2) receptor agonists [Cys(Et)(2,7)] hCGRPalpha and [Cys(Acm)(2,7)] hCGRPalpha were considerably smaller than the response to CGRP. These responses were abolished in chloride-free buffer and were TTX sensitive. Atropine, doxantrazole, and indomethacin did not block the effects of CGRP or the CGRP(2) agonists. The response to [Cys(Et)(2,7)] hCGRPalpha was not affected by prior desensitization of the CGRP receptor and vice versa. Inflamed rats had a similar secretory response to CGRP (I(sc), EC(50) 15 nM) and [Cys(Et)(2,7)] hCGRPalpha as control tissues, while being hyporesponsive to carbachol. CGRP application increased electrical conductance of inflamed preparations. Taken together, these data suggest that CGRP may play an important role in the maintenance of host defense in colitis through an apparently novel CGRP receptor located on the colonic enterocyte.
Esfandyari
T
T
Neuroscience and Gastrointestinal Research Groups, Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
Macnaughton
W K
WK
Quirion
R
R
St Pierre
S
S
Junien
J L
JL
Sharkey
K A
KA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D004553:Electric Conductivity; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D018015:Receptors, Calcitonin Gene-Related Peptide; D013779:Tetrodotoxin; D014302:Trinitrobenzenesulfonic Acid; D015740:Calcitonin Gene-Related Peptide