The possible role of substance P in mediating inflammation in inflammatory bowel disease (IBD) was evaluated by blocking the substance P (NK-1) receptor in an acute animal model. Ethanol and zymosan were administered via the rectum into the colon in anesthetized male Sprague-Dawley rats to induce the model. To assess the role of substance P, 5mg/kg of CP-96,345 was administered subcutaneously thirty minutes prior to induction of IBD and every hour for three hours, at which time testing was begun. In another group of rats, 3 00mug/kg of an antisense oligonucleotide targeted at NK-1 receptor mRNA was administered intraperitoneally twice daily for seven days prior to induction of IBD. Histological sections revealed an infiltration of inflammatory cells in the colons after ethanol/zymosan treatment. Plasma extravasation values in rats treated with ethanol/zymosan were significantly higher than in controls treated only with saline (P < 0.0001) or saline and ethanol (P = 0.0041). In ethanol/zymosan treated rats, those administered CP-96,345 had plasma extravasation values which were significantly less than in ethanol/zymosan treated controls (P < 0.0001). Administration of the antisense targeted at NK-1 receptor mRNA resulted in lower levels of plasma extravasation compared with controls (P < 0.01). NK-1 receptors may be involved in the expression of symptoms as a component of inflammation in IBD.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.79023 |
| Date | January 2002 |
| Creators | Landau, Anne M. |
| Contributors | Henry, James L. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001976401, proquestno: AAIMQ88238, Theses scanned by UMI/ProQuest. |
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