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Age-dependent decrease in the hepatic uptake and biliary excretion of ouabain in rats.

M Ohta1, S Kanai, Y Sato

  • 1First Laboratory of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.

Biochemical Pharmacology
|March 1, 1988
PubMed
Summary
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Biliary excretion of ouabain decreases with age in rats due to reduced hepatic uptake. This age-related decline in ouabain transport is linked to decreased hepatocyte plasma membrane protein mobility.

Area of Science:

  • Hepatobiliary Transport
  • Aging Research
  • Pharmacokinetics

Background:

  • Ouabain (a cardiac glycoside) is eliminated via biliary excretion.
  • Age-related changes can affect drug metabolism and transport.
  • Understanding these changes is crucial for drug efficacy and safety.

Purpose of the Study:

  • To investigate the effect of age on the biliary excretion of intravenously injected ouabain in rats.
  • To determine the relationship between age and hepatic uptake velocity of ouabain.
  • To explore the role of hepatocyte plasma membrane function in age-dependent transport changes.

Main Methods:

  • Intravenous injection of ouabain in male and female Wistar rats of different ages.
  • Measurement of biliary recovery of ouabain over time.

Related Experiment Videos

  • Determination of hepatic uptake velocity using isolated hepatocytes.
  • Kinetic analysis (Vmax, Km) of ouabain uptake in young and old rats.

    • Main Results:

    • Biliary recovery of ouabain significantly decreased with age in both male and female rats.
    • Hepatic uptake velocity of ouabain showed a linear decrease with increasing age.
    • Kinetic studies revealed a significantly lower Vmax in old rats, indicating reduced uptake capacity, while Km remained similar.
    • A strong negative correlation was observed between age and ouabain uptake velocity.

    Conclusions:

    • The age-dependent decline in biliary ouabain excretion is primarily attributed to reduced hepatic uptake.
    • Decreased lateral mobility of hepatocyte plasma membrane proteins may contribute to impaired hepatobiliary transport in aged rats.
    • These findings highlight the impact of aging on drug transport and cellular membrane function.