UP-REGULATION OF SECRETIN RECEPTOR GENE-EXPRESSION IN RAT CHOLANGIOCYTES AFTER BILE-DUCT LIGATION

Secretin stimulates ductular bile secretion by binding to receptors on intrahepatic bile duct epithelial cells (i.e., cholangiocytes). In th e rat, this choleretic effect increases after bile duct ligation (BDL) . Although cholangiocyte proliferation induced by BDL contributes to s ecretin-induced hypercholeresis, the mechanisms modulating these alter ations in secret-ininduced ductular bile secretion are obscure. Thus w e studied the expression of secretin receptor mRNA (SR-mRNA) in purifi ed liver cells from normal and BDL rats. Northern blot analysis and RN ase protection assays with mRNA from purified liver cells demonstrated SR-mRNA only in cholangiocytes; moreover, SR gene expression showed a seven- to ninefold increase in individual cholangiocytes from BDL rat s compared with controls. This increase in SR-mRNA expression was rela ted to a similar increase in the rate of transcription of SR-mRNA in c holangiocytes from BDL rats. Thus our studies indicate that 1) SR-mRNA is detected in liver only in cholangiocytes; 2) BDL causes an increas e in SR-mRNA in individual cholangiocytes; and 3) the increase in SR-m RNA after BDL is partly related to an increase in the rate of transcri ption of SR-mRNA by cholangiocytes after BDL. Our data suggest that up regulation of the SR gene may contribute to secretin-induced hyperchol eresis.