Abstract
Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification. Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP8-37), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP8-37 or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2617-2624 |
| Number of pages | 8 |
| Journal | Life Sciences |
| Volume | 71 |
| Issue number | 22 |
| DOIs | |
| State | Published - Oct 18 2002 |
| Externally published | Yes |
Fingerprint
Keywords
- Acid-induced duodenal villous injury
- CGRP
- Ruthenium red
- Substance P
ASJC Scopus subject areas
- Pharmacology
Cite this
Ruthenium red-sensitive cation channels, but not calcitonin gene-related peptide or substance P-mediated mechanisms, protect duodenal villi against acid-induced damage. / Leung, Felix W.; Iwata, Fumihiro; Kao, John; Seno, Kyoji; Itoh, Makoto; Leung, Joseph.
In: Life Sciences, Vol. 71, No. 22, 18.10.2002, p. 2617-2624.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ruthenium red-sensitive cation channels, but not calcitonin gene-related peptide or substance P-mediated mechanisms, protect duodenal villi against acid-induced damage
AU - Leung, Felix W.
AU - Iwata, Fumihiro
AU - Kao, John
AU - Seno, Kyoji
AU - Itoh, Makoto
AU - Leung, Joseph
PY - 2002/10/18
Y1 - 2002/10/18
N2 - Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification. Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP8-37), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP8-37 or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage.
AB - Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification. Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP8-37), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP8-37 or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage.
KW - Acid-induced duodenal villous injury
KW - CGRP
KW - Ruthenium red
KW - Substance P
UR - http://www.scopus.com/inward/record.url?scp=0037131609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037131609&partnerID=8YFLogxK
U2 - 10.1016/S0024-3205(02)02106-9
DO - 10.1016/S0024-3205(02)02106-9
M3 - Article
C2 - 12354580
AN - SCOPUS:0037131609
VL - 71
SP - 2617
EP - 2624
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 22
ER -