Cholecystokinin (CCK) down regulates PGE2 and PGI2 release in inflamed Guinea pig gallbladder smooth muscle cell cultures.
This study examines the hypothesis that cholecystitis down-regulates Guinea pig gallbladder (GPGB) smooth muscle cholecystokinin (CCK)-stimulated prostaglandin (PG) release. Guinea pig gallbladder from Control and 48 h bile duct ligated (BDL) animals were placed in cell culture and grown to confluence. The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA. BDL increased Guinea pig gallbladder cell culture basal PGE2 and PGI2 release which was in part due to increased COX-2 content. CCK incubation down-regulated BDL Guinea pig gallbladder cell culture release of 6-keto-PGF1alpha and PGE2 and down-regulated COX-2 content but did not alter the Control group. The decrease in CCK-mediated BDL cell Guinea pig gallbladder release may be an endogenous mechanism to limit physiologic derangements induced by increased endogenous gallbladder PG synthesis during early acute cholecystitis.
Myers
Stuart I
SI
Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA. simyers@vcu.edu
Bartula
Lori L
LL
Colvin
Mary P
MP
Parkman
Henry P
HP
D000818:Animals; D002478:Cells, Cultured; D002764:Cholecystitis / Q000201:enzymology / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D015777:Eicosanoids / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D019746:Intramolecular Oxidoreductases / Q000032:analysis; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D015777:Eicosanoids; D002766:Cholecystokinin; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D015232:Dinoprostone