Role of PGE2on gallbladder muscle cytoprotection of guinea pigs

Abstract

H2O2and taurochenodeoxycholic acid (TCDC) impair the contraction induced by CCK-8, ACh, and KCl without affecting the actions of PGE2and damage functions of membrane proteins except for PGE2receptors. The aim of this study was to examine whether the preserved PGE2actions contribute to cytoprotective mechanisms against reactive oxygen species. Muscle cells from guinea pig gallbladder were obtained by enzymatic digestion. Levels of lipid peroxidation and activities of SOD and catalase were determined by spectrophotometry. Pretreatment with PGE2prevented the inhibition of H2O2or TCDC on agonist (CCK-8, ACh, and KCl)-induced contraction and reduced the expected increase in lipid peroxidation and activities of catalase and SOD caused by H2O2and TCDC. Incubation with CCK-8 for 60 min desensitized CCK-1 receptors up to 30 min, whereas no receptor desensitization was observed after PGE2pretreatment. Cholesterol-rich liposome treatment enhanced the inhibition of H2O2and TCDC on agonists-induced contraction, including that of PGE2. Pretreatment with PGE2before H2O2and TCDC did not completely block their inhibition on agonist-induced contraction. Cholesterol-rich liposome treatment impaired the expected increase in catalase activities in response to PGE2. We conclude that pretreatment with PGE2prevents the muscle cell damage caused by H2O2and TCDC due to the resistance of PGE2receptors to agonist-induced desensitization. The preservation of PGE2receptors may be designed to conserve these cytoprotective functions that are, however, impaired by the presence of excess cholesterol in the plasma membrane.