Evaluation of prostaglandin-receptors in human and rat liver: interspecies differences at the prostaglandin receptor-level.
The properties of PGE1-, PGE2- and iloprost (stable PGI2-analogue)-binding sites on normal human and rat liver surface cell membranes were investigated. The specific binding of [3H]PGE1 to human (rat) liver surface cell membranes could be displaced most effectively by unlabeled PGE1 (IC-50:2.5 +/- 1.7, (6.1 +/- 2.1) microM) and the specific binding of [3H]PGE2 by unlabeled PGE2 (IC-50: 1.9 +/- 0.9 (2.0 +/- 0.8) microM. The Scatchard analysis on [3H]PGE1- as well as on [3H]iloprost-binding was curvilinear whereas it was clearly linear on [3H]PGE2-binding in both the species. The high-affinity [3H]PGE1-sites showed a Bmax of 36.3 +/- 5.2 (21.3 +/- 4.3) fmol/mg protein and a Kd of 2.1 +/- 1.8 (1.9 +/- 0.7) nM, the low-affinity [3H]PGE1-sites a Bmax of 93.4 +/- 18.2 (86.1 +/- 13.2) fmol/mg protein and a Kd of 10.5 +/- 2.9 (15.1 +/- 3.2) nM. The high-affinity [3H]iloprost-sites exhibited a Bmax of 71.4 +/- 13.9 (35.9 +/- 8.2) fmol/mg protein and a Kd of 4.1 +/- 1.2 (1.7 +/- 1.8) nM, the low-affinity [3H]iloprost-sites a Bmax of 217.3 +/- 42.1 (142.9 +/- 17.8) fmol/mg protein and a Kd of 16.3 +/- 4.9 (9.2 +/- 7.2) nM. The [3H]PGE2-sites showed a Bmax of 135.4 +/- 51.9 (38.8 +/- 7.4) fmol/mg protein and a Kd of 16.2 +/- 3.2 (2.5 +/- 1.2) nM. It is assumed that prostaglandins of the E-series are promising substances in the regulation of human and rat liver function since liver cells are able to bind reasonable amounts of these substances in a high affinity manner. However, interspecies differences in the affinity of the prostaglandins to their receptor-sites make it strange to assume that the same biological findings claimed several times for the rat liver are relevant for human too.
Virgolini
I
I
2nd Dept. of Nuclear Medicine, University of Vienna, Austria.
Müller
C
C
Hermann
M
M
Schütz
W
W
Sinzinger
H
H
D000818:Animals; D002462:Cell Membrane / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000493:pharmacokinetics; D006801:Humans; D016285:Iloprost; D066298:In Vitro Techniques; D008099:Liver / Q000032:analysis*; D011453:Prostaglandins / Q000493:pharmacokinetics; D011458:Prostaglandins E / Q000032:analysis / Q000493:pharmacokinetics; D011465:Prostaglandins, Synthetic / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000032:analysis*
D011453:Prostaglandins; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D011464:Epoprostenol; D016285:Iloprost