Increase in in vivo low-density lipoprotein (LDL) receptor binding after PGE1 and 13,14-dihydro-PGE1 treatment in rabbits

J Cardiovasc Pharmacol. 1993 Mar;21(3):503-6. doi: 10.1097/00005344-199303000-00023.

Abstract

In a total of 48 male rabbits, the influence of PGE1 and its metabolite, 13,14-dihydro-PGE1, on the liver LDL receptor was examined in vivo. One-half of the animals were fed a 1% cholesterol-enriched diet for 4 weeks, and the other 24 animals received their normal chow. One-third of the animals in both groups received PGE1 (5 micrograms/kg i.v.), another 13,14-dihydro-PGE1 (5 micrograms/kg i.v.), and the third was a control group receiving placebo injections only. The LDL-receptor activity (total LDL uptake by the liver vs. blood activity) after injection of radiolabelled [125I]LDL and LDL disappearance from plasma were quantified. In the cholesterol-supplemented animals, the radioactive LDL uptake was significantly (p < 0.001) lower compared to the control group. Both PGE1 and 13,14-dihydro-PGE1 caused a comparable increase in LDL uptake, the extent being more pronounced in the hypercholesterolemic animals. LDL disappearance in normocholesterolemic animals was much faster than in cholesterol-fed animals. Both of the PGs caused a faster disappearance, the extent being comparable. As a mechanism of action, an induction of messenger RNA for the receptor protein by the prostaglandins is discussed. These results indicate a hypolipidemic action of PGE1 and its biologically active metabolite at the receptor level.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / analogs & derivatives*
  • Alprostadil / pharmacology*
  • Animals
  • Cholesterol, Dietary
  • Hypercholesterolemia / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Rabbits
  • Receptors, LDL / drug effects*
  • Receptors, LDL / metabolism
  • Up-Regulation

Substances

  • Cholesterol, Dietary
  • Receptors, LDL
  • 13,14-dihydroprostaglandin E1
  • Alprostadil