ACUTE CHOLECYSTITIS POTENTIATES BRADYKININ-STIMULATED FIBROBLAST PROSTANOID RELEASE IN THE RABBIT

Gallbladder explants from control rabbits and rabbits subjected to bil e duct ligation (BDL) for 24 and 72 h (cholecystitis model) were place d in cell culture to determine the source for increased gallbladder pr ostanoid synthesis during cholecystitis. Cultures from control and 24 h BDL gallbladders grew spindle shaped fibroblasts which did not exhib it increased prostanoid synthesis. 72 h BDL gallbladder cell cultures grew large polygonal shaped cells which appeared to be 'stimulated fib roblasts' by light and electron microscopy and were associated with in creased basal and bradykinin stimulated 6-keto-PGF1alpha release and i ncreased content of prostacyclin synthase when measured by enzyme immu noassay and protein immunoblot analysis respectively. Use of bradykini n antagonists showed that the bradykinin BK2 subtype receptor was the most prominent in the 72 h BDL cell cultures. The 'stimulated fibrobla sts' were the source of bradykinin stimulated gallbladder 6-keto-PGF1a lpha synthesis in the inflamed rabbit gallbladder which was mediated b y the bradykinin B2 subtype receptor.