Effects of digitoxin and lithium, used as a marker of passive Na transport, on secretin-dependent bile flow in the pig.
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.
Grotmol
T
T
University of Oslo, Institute for Experimental Medical Research, Norway.
Buanes
T
T
Roeder
M
M
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D004074:Digitoxin / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008099:Liver / Q000201:enzymology; D009994:Osmolar Concentration; D012633:Secretin / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D014882:Water-Electrolyte Balance / Q000187:drug effects
D001639:Bicarbonates; D002712:Chlorides; D012633:Secretin; D008094:Lithium; D012964:Sodium; D004074:Digitoxin; D000254:Sodium-Potassium-Exchanging ATPase; D018021:Lithium Chloride; D005947:Glucose