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Am J Physiol Gastrointest Liver Physiol 275: G835-G846, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 4, G835-G846, October 1998

Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes

Alessandra Caligiuri1, Shannon Glaser1, Rebecca E. Rodgers1, Jo Lynne Phinizy1, Willie Robertson1, Emanuela Papa1, Massimo Pinzani2, and Gianfranco Alpini1,3

1 Department of Internal Medicine and Medical Physiology, Scott and White Hospital and Texas A&M University Health Science Center College of Medicine, and 3 Central Texas Veterans Health Care System, Temple, Texas 76504; and 2 Istituto di Medicina Interna, Universita' di Firenze, 50134 Firenze, Italy

We studied the expression of endothelin-1 (ET-1) receptors (ETA and ETB) and the effects of ET-1 on cholangiocyte secretion. The effects of ET-1 on cholangiocyte secretion were assessed in normal and bile duct-ligated (BDL) rats by measuring 1) basal and secretin-induced choleresis in vivo, 2) secretin receptor gene expression and cAMP levels in small and large cholangiocytes, and 3) luminal expansion in response to secretin in intrahepatic bile duct units (IBDU). ETA and ETB receptors were expressed by small and large cholangiocytes. ET-1 had no effect on basal bile flow or bicarbonate secretion in normal or BDL rats but decreased secretin-induced bicarbonate-rich choleresis in BDL rats. ET-1 decreased secretin receptor gene expression and secretin-stimulated cAMP synthesis in large cholangiocytes and secretin-induced luminal expansion in IBDU from normal or BDL rats. The inhibitory effects of ET-1 on secretin-induced cAMP synthesis and luminal duct expansion were blocked by specific inhibitors of the ETA (BQ-610) receptor. ET-1 inhibits secretin-induced ductal secretion by decreasing secretin receptor and cAMP synthesis, two important determinants of ductal secretion.

biliary epithelium; bile duct ligation; adenosine 3',5'-cyclic monophosphate; secretin receptor


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