Acid-sensing pathways of rat duodenum.
We tested the hypothesis that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide (NO). Laser-Doppler flowmetry was used to measure duodenal blood flow in urethan-anesthetized rats. Duodenal mucosa was superfused with pH 7. 0 buffer with capsaicin or bradykinin or was acid challenged with pH 2.2 solution, with or without vanilloid receptor antagonists, a CGRP receptor antagonist, an NO synthase (NOS) inhibitor, or a cyclooxygenase inhibitor. The selective vanilloid receptor antagonist capsazepine (CPZ) dose dependently inhibited the hyperemic response to acid and capsaicin but did not affect bradykinin-induced hyperemia. Ruthenium red was less inhibitory than capsazepine. Selective ablation of capsaicin-sensitive nerves, CGRP-(8-37), and N(G)-nitro-L-arginine methyl ester inhibited acid-induced hyperemia, but indomethacin did not. We conclude that luminal acid, but not bradykinin, stimulates CPZ-sensitive receptors on capsaicin-sensitive afferent nerves of rat duodenum. Activation of these receptors produces vasodilation via the CGRP-NO pathway but not via the cyclooxygenase pathway. Acid appears to be the endogenous ligand for duodenal vanilloid receptors.
Akiba
Y
Y
CURE: Digestive Diseases Research Center, Los Angeles, California 90073, USA.
Guth
P H
PH
Engel
E
E
Nastaskin
I
I
Kaunitz
J D
JD
D000143:Acids / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000502:physiology*; D004386:Duodenum / Q000098:blood supply / Q000294:innervation* / Q000378:metabolism*; D006940:Hyperemia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D000143:Acids; D011955:Receptors, Drug; C071423:capsazepine; D002211:Capsaicin; D001920:Bradykinin