Acute cholecystitis potentiates bradykinin stimulated fibroblast prostanoid release in the rabbit

Gallbladder explants from control rabbits and rabbits subjected to bile duct ligation (BDL) for 24 and 72 h (cholecystitis model) were placed in cell culture to determine the source for increased gallbladder prostanoid synthesis during cholecystitis. Cultures from control and 24 h BDL gallbladders grew spindle shaped fibroblasts which did not exhibit increased prostanoid synthesis. 72 h BDL gallbladder cell cultures grew large polygonal shaped cells which appeared to be 'stimulated fibroblasts' by light and electron microscopy and were associated with increased basal and bradykinin stimulated 6-keto-PGF1 alpha release and increased content of prostacyclin synthase when measured by enzyme immunoassay and protein immunoblot analysis respectively. Use of bradykinin antagonists showed that the bradykinin BK2 subtype receptor was the most prominent in the 72 h BDL cell cultures. The 'stimulated fibroblasts' were the source of bradykinin stimulated gallbladder 6-keto-PGF1 alpha synthesis in the inflamed rabbit gallbladder which was mediated by the bradykinin B2 subtype receptor.