Kinetics of prostaglandin E metabolism in isolated hepatocytes

The kinetics of prostaglandin E metabolism were investigated in isolated hepatocytes from male Sprague-Dawley rats. [³H] Prostaglandin E₁ or [³H]prostaglandin E₂ was incubated with cells in suspension, aliquots were collected over time and samples extracted and chromatographed using reverse-phase high-performance liquid chromatography. Both prostaglandins E₁ and E₂ were rapidly metabolized by the hepatocytes and at low prostaglandin E concentrations (10^-12 M) both have similar apparent half-lives (prostaglandin E₁, 1.24; prostaglandin E₂, 1.68 min). Disappearance of counts from prostaglandin E₁ and E₂ fractions was accompanied by the appearance of counts in earlier fractions of the chromatograms, consistent with metabolism to compounds which are more polar than the native prostaglandins. The half-life for prostaglandin E₁ was unchanged over a prostaglandin E₁ concentration range of 10^-12 to 10^-6 M. In contrast, increasing prostaglandin E₂ concentration resulted in a prolonged half-life over the same concentration range. Decreasing cell concentrations from 5 · 10⁶ to 5 · 10⁵ cells/ml resulted in decreases in the rates of metabolism of both prostaglandins E₁ and E₂.