Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Andre, E. et al.

E. Andre, D. Gazzieri, E. Bardella, J. Ferreira, M.A. Mori, V.V. Saul, M. Bader, J.B. Calixto, R. De Giorgio, R. Corinaldesi, P. Geppetti, M. Trevisani,

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

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.[1]

References

Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder. 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., Trevisani, M. Gut (2008) [Pubmed]

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