Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.
OBJECTIVE
To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA).


METHODS
Seven patients with irritable bowel syndrome.


METHODS
The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa.


RESULTS
Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa.


CONCLUSIONS
The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase.
Casellas
F
F
Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain.
Mourelle
M
M
Papo
M
M
Guarner
F
F
Antolin
M
M
Armengol
J R
JR
Malagelada
J R
JR
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003109:Colonic Diseases, Functional / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D015777:Eicosanoids / Q000032:analysis; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis*; D010477:Perfusion
D001647:Bile Acids and Salts; D015777:Eicosanoids; D009566:Nitrates; D003840:Deoxycholic Acid; D009569:Nitric Oxide