Cellular communication inside the liver. Binding, conversion and metabolic effect of prostaglandin D2 on parenchymal liver cells.
The major eicosanoid produced within the rat liver, prostaglandin (PG) D2, wa studied for its ability to interact with the various liver cell types. It appeared that PGD2 bound specifically to parenchymal liver cells, whereas the binding of PGD2 to Kupffer and endothelial liver cells was quantitatively unimportant. Maximally 700 pg of PGD2/mg of parenchymal-cell protein could be bound by a high-affinity site (1 x 10(6) PGD2-binding sites/cell). The recognition site for PGD2 is probably a protein because trypsin treatment of the cells virtually abolished the high-affinity binding. High-affinity binding of PGD2 was a prerequisite for the induction of a metabolic effect in isolated parenchymal liver cells, i.e. the induction of glycogenolysis. High-affinity binding of PGD2 by parenchymal cells was coupled to the conversion of PGD2 into three metabolites, whereas no conversion of PGD2 by Kupffer and endothelial liver cells was noticed. The temperature-sensitivity of the conversion of PGD2 was consistent with a conversion of PGD2 on or in the vicinity of the cell membrane. One of the PGD2 metabolites could be identified as 9 alpha, 11 beta-PGF2. It can be calculated that the conversion rate of PGD2 by parenchymal liver cells exceeds the production rate of PGD2 by Kupffer plus endothelial liver cells, indicating that PGD2 is meant to exert its activity within the liver. The present finding that PGD2 formed by the non-parenchymal liver cells is recognized by a specific receptor on parenchymal liver cells and that binding, conversion and metabolic effect of PGD2 are interlinked by this receptor provides further support for the specific role of PGD2 in the intercellular communication in the liver.
Kuiper
J
J
Division of Biopharmaceutics, University of Leiden, The Netherlands.
Zijlstra
F J
FJ
Kamps
J A
JA
Van Berkel
T J
TJ
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D015230:Prostaglandin D2 / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000527:Alprostadil; D005947:Glucose; D015232:Dinoprostone; D015230:Prostaglandin D2