Prostanoids and leukotrienes in experimental feline cholecystitis

Current information suggests that arachidonic acid metabolites are involved in the development of cholecystitis. The purpose of this study was to evaluate eicosanoid formation during the development of experimental cholecystitis in cats. Lysophosphatidylcholine is found in the gallbladders of patients with cholecystitis and is known to be a cytolytic, membrane-damaging substance. Anesthetized cats underwent gallbladder perfusion with and without 1.5 mmol/L lysophosphatidylcholine. Additional experiments were performed when calcium ionophore were added to the perfusates and experiments were performed when cats were treated with indomethacin and underwent perfusion with lysophosphatidylcholine. Changes in the gallbladder were determined by evaluating mucosal water transport as measured by determining the changes in concentration in a nonabsorbable marker, by protein secretion and by beta-glucuronidase accumulation in gallbladder tissue as an index of inflammation. Eicosanoid formation was evaluated by measuring perfusate concentrations and gallbladder homogenate concentrations by radioimmunoassay of prostaglandin E, 6 keto prostaglandin F1 alpha, leukotriene B4 and leukotriene C4. Lysophosphatidylcholine perfusion reversed the control patterns of absorption and produced water exsorption, produced an efflux of protein into the perfusate and increased beta-glucuronidase activity. These changes were accompanied by increased production of prostaglandin E and 6 keto prostaglandin F1 alpha in gallbladder perfusate and homogenate. The concentration of leukotriene C4 in gallbladder effusate was increased by lysophosphatidylcholine when compared with control values. Indomethacin inhibited the protein efflux, decreased beta-glucuronidase levels and decreased prostaglandin E and 6 keto prostaglandin F1 alpha formation when compared with values produced by lysophosphatidylcholine alone. Cyclooxygenase inhibition did not alter the secretion of water into the gallbladder or perfusate leukotriene C4 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)