Bradykinin and not cholecystokinin stimulates exaggerated prostanoid release from the inflamed rabbit gallbladder

Abstract

The relationship of bradykinin and cholecystokinin (CCK) to inflamed gallbladder prostanoid synthesis and release was examined in rabbits treated with common bile duct ligation (BDL) for 24 or 72 h. Gallbladders removed from control and BDL groups were incubated in oxygenated Krebs buffer at 37 °C (pH 7.4) for 60 min. The slices were then placed every 20 min in vials containing increasing doses of bradykinin (30–3000 ng) or CCK (30–1000 ng). Incubation fluid was analyzed by RIA for 6-keto-prostaglandin (PG)F 1α (PGI 2 metabolite), PGE 2 and thromboxane (TX) B 2. Bradykinin stimulated control gallbladder 6-keto-PGF 1α and PGE 2 release was modest. Gallbladders from 24- and 72-h BDL groups released 3- to 10-fold higher levels of 6-keto-PGF 1α and PGE 2 (not TXB 2) following bradykinin stimulation when compared to controls, which was abolished with indomethacin pretreatment. CCK did not stimulate gallbladder prostanoid release in the control or BDL groups. These data show that bradykinin and not CCK stimulated PGI 2 and PGE 2 release from inflamed rabbit gallbladder. Increased BDL gallbladder PGI 2 release may be prolonged or augmented by bradykinin as gallbladder distention and progressive acute inflammation stimulate local bradykinin formation.