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Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder

Item Type:Article
Title:Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder
Creators Name:Andre, E., Gazzieri, D., Bardella, E., Ferreira, J., Mori, M.A., Saul, V.V., Bader, M., Calixto, J.B., De Giorgio, R., Corinaldesi, R., Geppetti, P. and Trevisani, M.
Abstract:Background & AIMS: We have recently described that bradykinin B2 receptors are expressed in the human gallbladder and that their activation induces a powerful contraction, especially in acute cholecystitis tissues. Here we investigated the role of B1 receptor in the contractility of control and inflamed human gallbladder. METHODS: Strips of human gallbladder from either acute gallstone cholecystitis or elective gastro-entero-pancreatic surgery (control) were assessed in vitro and processed for reverse-transcription polymerase chain reaction (PCR) analysis. Cumulative concentration-response curves with the selective B1 receptor agonist, Lys-Des-Arg9-bradykinin, cholecystokinin and carbachol were performed in control and cholecystitis specimens. RESULTS: Lys-Des-Arg9-bradykinin concentration-dependently contracted strips of control gallbladders and its motor effect was higher in inflamed gallbladders. Lys-Des-Arg9-bradykinin-induced contraction was not altered by the pre-treatment with: the selective bradykinin B2 receptor antagonist, HOE140 (1 microM), the NK1 (SR140333), NK2 (SR48968) and NK3 (SR142801) tachykinin receptor antagonists (all 1 microM), the muscarinic acetylcholine receptor antagonist, atropine (1 microM) and the cyclooxygenase inhibitor, indomethacin (5 microM). In contrast, Lys-Des-Arg9-bradykinin-induced motor response was significantly reduced by the selective B1 receptor antagonist, R-715. Finally, quantitative real-time PCR analysis indicated that B1 receptor mRNA levels were significantly higher in cholecystitis smooth muscle specimens, when compared to that observed in control tissues. CONCLUSIONS: bradykinin B1 receptor has an important role as spasmogen of human gallbladder and selective antagonists of the B1 receptor may represent a valid therapeutic option to control pain in patients with acute cholecystitis.
Keywords:B1 receptor, Bradykinin, Cholecystitis, Contraction, Human gallbladder
Publisher:BMJ Publishing Group
Page Range:628-633
Date:May 2008
Official Publication:https://doi.org/10.1136/gut.2006.103200
PubMed:View item in PubMed

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