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
- human gallbladder