Regulation of eicosanoid synthesis in fibroblasts from inflamed gallbladders.
Gallbladder cell cultures obtained from rabbits subjected to sham or 72 h of bile duct ligation (72 h BDL, cholecystitis model) were incubated with calcium ionophore (A23187), dibutyryl cAMP (cAMP), and phorbol 12,13-diacetate (phorbol) to determine the intracellular signal transduction mechanisms responsible for increased inflamed gallbladder eicosanoid synthesis. Incubation of sham and 72 h BDL cell cultures with A23187 or phorbol significantly increased, whereas cAMP decreased, release of 6-keto-PGF1 alpha, PGE2, thromboxane B2 (measured by enzyme immunoassay) in a dose-related manner. Seventy-two-hour BDL cell cultures contained a specific 2-fold increased level of prostacyclin synthase compared to sham cell cultures which was not altered by preincubation with A23187, phorbol or cAMP. These findings suggest that increased PGI2 release in the sham and inflamed cell cultures following A23187 and phorbol stimulation was mediated in part via the inositol triphosphate pathway and protein kinase C activation and was not associated with altered cyclooxygenase or prostacyclin synthase content.
Myers
S I
SI
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, USA.
Evans
C T
CT
Bartula
L
L
Riva
A
A
Kalley-Taylor
B
B
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002764:Cholecystitis / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases; D007476:Ionophores / Q000494:pharmacology; D007535:Isomerases / Q000378:metabolism; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction; D013929:Thromboxane B2 / Q000096:biosynthesis
D015777:Eicosanoids; D007476:Ionophores; D010703:Phorbol Esters; C008874:phorbol-12,13-diacetate; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003994:Bucladesine; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D015232:Dinoprostone