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Expression and functional pharmacology of the bradykinin B1 receptor in the normal and inflamed human gallbladder
  1. E Andre1,
  2. D Gazzieri1,
  3. E Bardella2,
  4. J Ferreira3,
  5. M A Mori4,
  6. V V Saul4,
  7. M Bader4,
  8. J B Calixto5,
  9. R De Giorgio6,
  10. R Corinaldesi6,
  11. P Geppetti1,
  12. M Trevisani1
  1. 1 Department of Experimental and Clinical Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy
  2. 2 Department of Surgery, University of Ferrara, Ferrara, Italy
  3. 3 Department of Chemistry, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
  4. 4 Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
  5. 5 Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
  6. 6 Department of Internal Medicine and Gastroenterology, University of Bologna, Italy
  1. Ms E Andre, Department of Experimental & Clinical Medicine, Pharmacology Unit, University of Ferrara, Via Fossato di Mortara 19, 44100 Ferrara, Italy; andre.eunice{at}unife.it

Abstract

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-Arg9-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-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 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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Footnotes

  • Competing interests: None.

  • Funding: Grant support: the study was supported by a grant from MURST. JF thanks FAPERGS for the ARD fellowship. This work was partially supported by grants from the Italian Ministry of Education, University and Research (CCOFIN Project no. 2004062155 to RDeG)

  • Patient consent: All patients gave their informed consent prior to surgery.

  • Ethics approval: The present study was approved by the Ethical Committee of the University of Ferrara.

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