Effects of digitoxin and lithium, used as a marker of passive Na transport, on secretin‐dependent bile flow in the pig

Abstract

The present study was performed in anaesthetized pigs, and the first aim was to assess the role of Na,K-ATPase in secretin-dependent biliary HCO3 secretion (JbHCO3). Intra-arterial administration of the cardiac glycoside digitoxin (0.2 mg/kg-1) reduced hepatic Na K-ATPase activity, JbHCO3 and secretin-dependent bile flow by 24, 55 and 34% respectively. In the second part of this study lithium (Li) was used as a marker of passive Na transport to assess the electrochemical gradient for Na flux into bile duct lumen during secretin-stimulated bile flow and impeded biliary osmotic water flow by i.v. infusion of glucose. At plasma glucose 85 (73-96) mmol l-1, bile [Na] and [Li] exceeded their concentrations in plasma by 57 and 47% respectively. By using the Nernst equation, transepithelial potential difference (PD) during hyperglycaemia was estimated to be -6.2 (0 to -10.8) mV (ductal lumen negative), which corresponds to a [Li]bile/[Li]plasma ratio of 1.3 (1.0-1.5). The ratio was not significantly different from the observed [Li]bile/[Li]plasma ratio of 1.4 (1.3-1.5). It is concluded (1) that Na, K-ATPase is necessary for JbHCO3, probably by sustaining the cell membrane PD (cell interior negative) which is a driving force for apical electrogenic HCO3 secretion, and (2) transepithelial Li (and hence Na) flux is driven solely by the negative transcellular PD during secretin-stimulated bile flow in the pig.