title: [Involvement of endogenous tachykinins in the development of jejunal mucosa injury induced by on-steroidal anti-inflammatory drugs].
abstract: Previous studies have shown that tachykinins, the largest family of neuropeptides, affect the development of mucosal damage in the stomach and colon. The aim of the study was to assess the influence of tachykinins receptors antagonists on the development of the mucosa injury in the proximal and distal jejunum.
  
  
  METHODS
  Mucosal damage was induced by administration of non-steroidal anti inflammatory drugs (NSAIDs), indomethacin, celecoxib or combination of indomethacin plus celecoxib given intragastrically. NK-1 receptor antagonist (SR 140333), NK-2 receptor antagonist (SR 48968) and NK-3 receptor antagonist (SR 142801) were administered intraperitoneally twice, 30 min before treatment with NSAID and again 24 h later, 30 min before the end of the experiment.
  
  
  RESULTS
  Administration of indomethacin, a relatively selective inhibitor for cyclooxygenase-1 (COX-1), induced mucosal lesions in the jejunum. Lesions area in the distal jejunum was 8-fold bigger than in the proximal jejunum. This effect was associated with a significant reduction in mucosal blood flow and an increase in mucosal concentration of pro-inflammatory interleukin-1beta (IL-1beta). Celecoxib, selective inhibitor for COX-2 failed to induce mucosal lesions and did not affect the mucosal blood flow and IL-1beta concentration in the proximal and distal jejunum. In rats treated with a combination of indomethacin plus celecoxib, ulcers reached maximal area. This effect was associated with the highest concentration of mucosal IL-1beta and maximal reduction in mucosal blood flow. Administration of NK-1 receptor antagonist, SR 140333 reduced jejunal damage induced by indomethacin given alone or in combination with celecoxib. This effect was associated with significant reduction in mucosal concentration of IL-1beta. Effect of SR 140333 on mucosal blood flow was statistically insignificant. Neither NK-2 nor NK-3 receptor inhibitor affected mucosal blood flow, IL-1beta concentration area of NSAIDs-induced mucosal damage in the jejunum.
  
  
  CONCLUSIONS
  Blockade of NK-1 receptor protects the jejunum against NSAIDs-induced mucosal injury and reduces local inflammation. This observation indicates the involvement of endogenous tachykinins in deleterious effects of NSAID.
authors.affiliation: Zakład Fizjologii Klinicznej Katedry Fizjologii, Uniwersytet Jagielloński, Collegium Medicum w Krakowie.
authors.forename: Paweł
authors.initials: P
authors.lastname: Sendur
authors.forename: Piotr
authors.initials: P
authors.lastname: Ceranowicz
authors.forename: Ryszard
authors.initials: R
authors.lastname: Sendur
authors.forename: Jakub
authors.initials: J
authors.lastname: Cieszkowski
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Warzecha
authors.forename: Artur
authors.initials: A
authors.lastname: Dembiński
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007579:Jejunal Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052016:Mucositis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D015320:Tachykinins / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018039:Receptors, Tachykinin; D015320:Tachykinins