Bradykinin B₂ receptors mediate contraction in the normal and inflamed human gallbladder in vitro

Background & Aims: The components of the kinin system, including kinongens, kininogenases, and B₂ and B₁ receptors, are expressed and activated during inflammation. Here, we investigated the expression of the kinin B₂ receptor messenger RNA, kininogen and kallikrein immunoreactivity, and the ability of kinins to contract control and inflamed gallbladders in vitro. Methods: Human gallbladders, obtained from patients undergoing cholecystectomy either for acute cholecystitis secondary to gallstone disease or during elective gastro-enteropancreatic surgery (controls), were processed for reverse-transcription polymerase chain reaction analysis, kallikrein and kininogen immunohistochemistry, binding studies, and in vitro contractility studies. Results: Tissue expression of B₂ receptor messenger RNA and specific binding of [³H]-bradykinin increased significantly in acute cholecystitis compared to controls. Kallikrein immunoreactivity was detected in the epithelium and infiltrating leukocytes, whereas kininogen immunoreactivity in the lumen of blood vessels and interstitial space. Bradykinin contracted isolated strips of control and acute cholecystitis gallbladders. In acute cholecystitis tissue, efficacy of bradykinin was higher than that of control gallbladders and similar to that of cholecystokinin. The contraction induced by bradykinin was significantly attenuated by B₂ receptor antagonism but not by cyclooxygenase inhibition and B₁, muscarinic, or tachykinin receptor antagonism. Conclusions: All the components of the kinin system are expressed in the human gallbladder. Bradykinin is a powerful spasmogen via B₂ receptor activation in the normal and, especially, in the inflamed human gallbladder.