Molecular and Pathological Studies on P-glycoproteins in the Mechanisms of Bile Secretion

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The localization of P-glycoproteins in cholestatic conditions has been examined by immunohistochemistry to elucidate its functional significance in the mechanisms of bile secretion. The reaction products ofP-glycoproteins (mdr1,2) were observed on bile canaliculi in control rats. In intrahepatic cholestasis induced by cytochalasin B and lithocholic acid, the reaction products were decreased, and bile canalicular contractions were remarkably impaired with dilatation of the canaliculi. On the other hand, the activities of P-glycoproteins were increased on 1,3 day after common bile duct ligation, and dimished on day 7. The expression of mdr1b, mdr2 and cMOAT genes in obstructive jaundice was assessed by Southern blotting for RT-PCR products. The expression of mdr1b, mdr2 and cMOAT was detected in control rats. The bile duct obstruction induced mdr1b, mdr2 mRNA expressions on day 1,3,7 after ligation, while the expression of cMOAT mRNA was not affected. These findings suggest that mdr2 as well as mdr1 may be associated with the mechanisms of bile secretion.