Upregulation of secretin receptors on cholangiocytes after bile duct ligation

Secretin not only increases ductular bile secretion in vivo in rats after b ile duct ligation (BDL) [1], but also increases cAMP levels and stimulates exocytosis in isolated cholangiocytes [2]. Although we have previously repo rted that secretin receptor mRNA was upregulated in cholangiocytes after BD L [3], the cholangiocyte secretin receptor has not been functionally charac terized 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 i n a rapid, reversible, and temperature-dependent manner. While receptors on cholangiocytes from normal and BDL rats were functionally and biochemicall y identical, receptor density on cholangiocytes was increased 5-fold follow ing BDL. The combination of increased cell number with increased functional secretin receptors per cell is due to the fact that cholangiocyte hyperpla sia represents a reactive response to a cholestatic condition and this effo rt on the part of the organism to maintain bile secretion, explains the inc reased hormone-responsive choleresis observed after BDL and may reflect an adaptive response of the organism to cholestasis. (C) 2001 Elsevier Science B.V. All rights reserved.