Sodium, hydrogen exchange type 1 and bile ductular secretory activity in the guinea pig.
Biliary epithelial cells (BECs) express different Na(+), H(+) exchange (NHE) isoforms. In this study, the potential role of NHE in ductular bile secretion is assessed. Experiments were performed in guinea pig perfused livers and isolated BECs. Inhibition of NHE was achieved by hypotonic stress and by using the unspecific NHE inhibitor, amiloride, or the specific NHE 1 inhibitor, cariporide (HOE 642). Hypotonic stress inhibited basal bile flow by 46% and prevented secretin stimulation of bile flow by reducing biliary bicarbonate output by 50%. Secretin increased bile flow from 3.7 +/- 0.8 microL/min/g to 4.78 microL/min/g (P <.01); subsequent exposure to hypotonic stress decreased secretin-stimulated bile flow by 35% and biliary bicarbonate secretion by approximately 50%. Inhibition of NHE by amiloride or cariporide resulted in a similar reduction of secretin-stimulated bile flow and bicarbonate secretion. Basal bile flow was unaffected by the NHE inhibitors. In isolated guinea pig BECs, regulatory volume decrease and inhibition of NHE was demonstrated after hypotonic stress under basal and secretin-stimulated conditions. In contrast, hypotonic exposure inhibited Cl(-), HCO(3)(-) exchange activity in isolated BECs only during basal conditions but incompletely after secretin stimulation. Our study shows that hypotonic stress inhibits basal bile flow in the guinea pig by inhibition of Cl(-), HCO(3)(-) exchange. NHE1 is not involved in basal bile formation. Increased choleresis after ductular stimulation by secretin depends on intact NHE1 activity. These data indicate that BEC volume changes have profound effects on biliary secretory function.
Hübner
C
C
Department of Medicine, University of Heidelberg, Heidelberg, Germany.
Stremmel
W
W
Elsing
C
C
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D004847:Epithelial Cells / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D007038:Hypotonic Solutions / Q000494:pharmacology; D007633:Keratins / Q000032:analysis; D008297:Male; D010477:Perfusion; D012633:Secretin; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D006146:Guanidines; D007038:Hypotonic Solutions; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D012633:Secretin; D007633:Keratins; D000584:Amiloride; C093373:cariporide