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 the rat, this choleretic effect increases after bile duct ligation (BDL). Although cholangiocyte proliferation induced by BDL contributes to secretin-induced hypercholeresis, the mechanisms modulating these alterations in secret-ininduced ductular bile secretion are obscure. Thus we studied the expression of secretin receptor mRNA (SR-mRNA) in purified liver cells from normal and BDL rats. Northern blot analysis and RNase 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 rats compared with controls. This increase in SR-mRNA expression was related to a similar increase in the rate of transcription of SR-mRNA in cholangiocytes from BDL rats. Thus our studies indicate that 1) SR-mRNA is detected in liver only in cholangiocytes; 2) BDL causes an increase in SR-mRNA in individual cholangiocytes; and 3) the increase in SR-mRNA after BDL is partly related to an increase in the rate of transcription of SR-mRNA by cholangiocytes after BDL. Our data suggest that upregulation of the SR gene may contribute to secretin-induced hypercholeresis.