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  • Title: Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder.
    Author: Andre E, Gazzieri D, Bardella E, Ferreira J, Mori MA, Saul VV, Bader M, Calixto JB, De Giorgio R, Corinaldesi R, Geppetti P, Trevisani M.
    Journal: Gut; 2008 May; 57(5):628-33. PubMed ID: 18182589.
    Abstract:
    BACKGROUND AND AIMS: It has recently been described that bradykinin B(2) 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 B(1) 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 B(1) receptor agonist, Lys-Des-Arg(9)-bradykinin, cholecystokinin and carbachol were performed in control and cholecystitis specimens. RESULTS: Lys-Des-Arg(9)-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 B(2) receptor antagonist, HOE140 (1 microM), the NK(1) (SR140333), NK(2) (SR48968) and NK(3) (SR142801) tachykinin receptor antagonists (all 1 microM), the muscarinic acetylcholine receptor antagonist, atropine (1 microM), and the cyclo-oxygenase inhibitor, indomethacin (5 microM). In contrast, the Lys-Des-Arg(9)-bradykinin-induced motor response was significantly reduced by the selective B(1) receptor antagonist, R-715. Finally, quantitative real-time PCR analysis indicated that B(1) receptor mRNA levels were significantly higher in cholecystitis smooth muscle specimens, when compared with that observed in control tissues. CONCLUSIONS: Bradykinin B(1) receptor has an important role as a spasmogen of human gallbladder, and selective antagonists of the B(1) receptor may represent a valid therapeutic option to control pain in patients with acute cholecystitis.
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