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Expression And Functional Pharmacology Of The Bradykinin B1 Receptor In The Normal And Inflamed Human Gallbladder
  1. Eunice Andre (andre.eunice{at}
  1. University of Ferrara, Italy
    1. David Gazzieri
    1. University of Ferrara, Italy
      1. Elisabetta Bardella
      1. University of Ferrara, Italy
        1. Juliano Ferreira
        1. Universidade Federal de Santa Maria, Brazil
          1. Marcelo A Mori
          1. Max Delbruck Center, Germany
            1. Vera V. Saul
            1. Max Delbruck Center, Germany
              1. Michael Bader
              1. Max Delbruck Center, Germany
                1. João B Calixto
                1. Universidade Federal de Santa Catarina, Brazil
                  1. Roberto De Giorgio
                  1. University of Bologna, Italy
                    1. Roberto Corinaldesi
                    1. University of Bologna, Italy
                      1. Pierangelo Geppetti
                      1. University of Ferrara, Italy
                        1. Marcello Trevisani
                        1. University of Ferrara, Italy


                          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 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 cyclooxygenase inhibitor, indomethacin (5 µM). 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.

                          • B1 receptor
                          • bradykinin
                          • cholecystitis
                          • contraction
                          • human gallbladder

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