Intracellular alkalinization stimulates bile flow and vesicular-mediated exocytosis in IPRL

Am J Physiol. 1993 Aug;265(2 Pt 1):G347-53. doi: 10.1152/ajpgi.1993.265.2.G347.

Abstract

Intracellular pH recovery from an acute alkaline load in rat hepatocytes is mediated by a Cl(-)-HCO3- exchanger, which is electroneutral, Na+ independent, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) sensitive. Stimulation of this Cl(-)-HCO3- exchanger requires intact microtubules, suggesting that vesicular transport may be required to activate this exchanger. To determine if intracellular alkalinization stimulates biliary HCO3- excretion and bile flow in the intact liver by vesicle-mediated exocytosis, isolated perfused rat livers (IPRL) were alkalinized by two protocols. Isohydric changes in CO2 and HCO3- concentrations induced transient increases in bile flow by 36% (P < 0.01), which were abolished by DIDS (0.01 mM), inhibited by pretreatment with colchicine (P = 0.01), but not affected by membrane depolarization with the K(+)-channel blocker BaCl2 (1 mM). Similarly, perfusion with 20 mM NH4Cl produced a 42% increase in bile flow (P < 0.01) and a 26% increase in biliary HCO3- excretion. Both the increases in bile flow and HCO3- excretion were almost completely blocked by DIDS and inhibited by pretreatment with colchicine (P < 0.01). Biliary excretion of horseradish peroxidase was also increased during intracellular alkalinization with either protocol (P < 0.01). These findings suggest that intracellular alkalinization stimulates bile flow and biliary HCO3- excretion. Microtubule-dependent vesicular-mediated exocytosis is involved in this response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / analogs & derivatives
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / pharmacology
  • Alkalies / metabolism*
  • Animals
  • Anions / antagonists & inhibitors
  • Anions / metabolism
  • Barium / pharmacology
  • Bicarbonates / metabolism
  • Bile / physiology*
  • Biological Transport / drug effects
  • Colchicine / pharmacology
  • Exocytosis*
  • Horseradish Peroxidase / metabolism
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Intracellular Membranes / metabolism*
  • Liver / metabolism*
  • Male
  • Potassium Channels / drug effects
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Alkalies
  • Anions
  • Bicarbonates
  • Potassium Channels
  • Barium
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
  • Horseradish Peroxidase
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Colchicine