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

Andre, E.; Gazzieri, D.; Bardella, E.; Ferreira, J.; Mon, M. A.; Saul, V. V.; Bader, M.; Calixto, J. B.; De Giorgio, R.; Corinaldesi, R.; Geppetti, P.; Trevisani, M.
May 2008
Gut;May2008, Vol. 57 Issue 5, p628
Academic Journal
BACKGROUND AND AIMS: It has recently been 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 the role of the B1 receptor in the contractility of control and inflamed human gallbladder was investigated. 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-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-Arg(9)-bradykinin-induced contraction was not altered by pretreatment with the selective bradykinin B2 receptor antagonist, HOE140 (1 μM), the NK1 (SR140333), NK2 (SR48968) and NK3 (SR142801) tachykinin receptor antagonists (all 1 μM), the muscarinic acetylcholine receptor antagonist, atropine (1 μM), and the cyclo-oxygenase inhibitor, indomethacin (5 μM). In contrast, the Lys-Des-Arg(9)-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 with that observed in control tissues. CONCLUSIONS: Bradykinin B1 receptor has an important role as a 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.


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