Increase in in vivo low-density lipoprotein (LDL) receptor binding after PGE1 and 13,14-dihydro-PGE1 treatment in rabbits.
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.
Sinzinger
H
H
Wilhelm Auerswald-Atherosclerosis Research Group (ASF) Vienna, Austria.
Virgolini
I
I
Li
S R
SR
Gerakakis
A
A
Fitscha
P
P
O'Grady
J
J
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002791:Cholesterol, Dietary; D006937:Hypercholesterolemia / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D002791:Cholesterol, Dietary; D011973:Receptors, LDL; C069881:13,14-dihydroprostaglandin E1; D000527:Alprostadil