Upregulation of secretin receptors on cholangiocytes after bile duct ligation

Secretin not only increases ductular bile secretion in vivo in rats after bile duct ligation (BDL) [1], but also increases cAMP levels and stimulates exocytosis in isolated cholangiocytes [2]. Although we have previously reported that secretin receptor mRNA was upregulated in cholangiocytes after BDL [3], the cholangiocyte secretin receptor has not been functionally characterized or quantified after BDL. In this work, we used a novel, photolabile and biologically active analogue of secretin to quantify and characterize secretin receptors on cholangiocytes isolated from normal and BDL rats. The cholangiocyte secretin receptor bound radioligand with high affinity and in a rapid, reversible, and temperature-dependent manner. While receptors on cholangiocytes from normal and BDL rats were functionally and biochemically identical, receptor density on cholangiocytes was increased 5-fold following BDL. The combination of increased cell number with increased functional secretin receptors per cell is due to the fact that cholangiocyte hyperplasia represents a reactive response to a cholestatic condition and this effort on the part of the organism to maintain bile secretion, explains the increased hormone-responsive choleresis observed after BDL and may reflect an adaptive response of the organism to cholestasis.