Thromboxane-prostanoid receptor expression and antagonism in dextran-sodium sulfate-induced colitis.
OBJECTIVE
In the current study of murine colitis, the potential roles of thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as much as thromboxane signaling has been implicated in human inflammatory bowel disease.


METHODS
Colitis was induced in C57BL/6 mice via ingestion of dextran sodium sulfate (DSS), with or without co-administration of the thromboxane synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost (2.5 mg/kg/day).


RESULTS
Immunohistochemistry of colonic tissue demonstrated a DSS-induced increase in TP receptor expression, but not of thromboxane synthase. Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS. Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation induced by DSS, with vapiprost allowing a smaller increase in colon weight per unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced alterations in intestinal transit.


CONCLUSIONS
In summary, TP receptor antagonism was more effective than thromboxane synthase inhibition in alleviating DSS-induced colitis in mice.
Carter
Patsy R
PR
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
McElhatten
Robert M
RM
Zhang
Songlin
S
Wright
William S
WS
Harris
Norman R
NR
D000818:Animals; D003092:Colitis / Q000139:chemically induced*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005769:Gastrointestinal Motility; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011517:Prothrombin Time; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism
D004791:Enzyme Inhibitors; D008689:Methacrylates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D016264:Dextran Sulfate; C034364:ozagrel