PGE0 inhibits collagen and glycosaminoglycan-synthesis in the rabbit arterial wall.
The influence of 13,14-dihydro-PGE1 (PGE0), a biologically active metabolite of PGE1, on collagen and glycosaminoglycan synthesis by the rabbit arterial wall was assessed and compared with the effect of PGE1. Collagen (COL) and glycosaminoglycan (GAG) synthesis was measured using 14C proline- and 35S-incorporation respectively and both were subsequently quantified by autoradiography. PGE1 decreased GAG-synthesis by 40%, while PGE0 caused a 25% decrease. COL-synthesis after PGE1 treatment was diminished by 35%, while the biologically active metabolite caused a drop of 30%. Five and 15 micrograms/kg doses of both compounds were almost equally effective, 1 microgram was without effect. These findings indicate that PGE0 shares the inhibitory effect of PGE1 on COL and GAG biosynthesis. This metabolite has about 60 to 70% of the biological activity of its parent compound PGE1. These results suggest that part of the effects of PGE1 in inhibiting extracellular matrix production could be due to its metabolite PGE0.
Rodrigues
M
M
Department of Nuclear Medicine, University of Vienna, Austria.
Sinzinger
H
H
Kritz
H
H
Peskar
B A
BA
O'Grady
J
J
Rogatti
W
W
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D006025:Glycosaminoglycans; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D003094:Collagen; C086635:prostaglandin E0; D000527:Alprostadil