Taurodeoxycholic acid stimulates rabbit gallbladder eicosanoid release.
Rabbit common bile duct ligation has been shown to concomitantly increase levels of gallbladder taurodeoxycholic acid and gallbladder eicosanoid release. This study examines the hypothesis that taurodeoxycholic acid, a known chemical mediator of gallbladder inflammation, stimulates endogenous gallbladder eicosanoid release. Male New Zealand white rabbits were anesthetized, gallbladders removed and perfused in vitro with Krebs-Henseleit buffer (pH 7.4, 37 degrees C) at 1 ml/min with increasing doses of taurodeoxycholic acid (0, 10, 30 and 100 mM) added to the perfusate. The effluent was collected at 15, 30, 60 and 120 min of perfusion and assayed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, and thromboxane B2 (TXB2) by enzyme immunoassay. Taurodeoxycholic acid increased gallbladder eicosanoid release in a dose-related manner with 6-keto-PGF1 alpha and PGE2 release 10-fold higher than TXB2. Indomethacin (1.5 mM) decreased gallbladder eicosanoid release by 50% in the gallbladders perfused with 30 mM taurodeoxycholic acid, demonstrating that the increased gallbladder eicosanoid release was due to de novo synthesis. These findings suggest that the increased release of gallbladder PGI2 and PGE2 described in animal models of cholecystitis may, in part, be related to increased gallbladder bile levels of taurodeoxycholic acid.
Myers
S I
SI
Department of Surgery, University of Texas Southwestern Medical Center, Dallas.
Riva
A
A
Kalley-Taylor
B
B
Bartula
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011817:Rabbits; D013657:Taurodeoxycholic Acid / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000032:analysis / Q000378:metabolism
D015777:Eicosanoids; D013657:Taurodeoxycholic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin