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Abstract
Prostaglandins (PG) produced by activated non-parenchymal liver cells regulate the function of parenchymal cells through six classes of G-protein-coupled receptors (-R): four receptor subtypes for PGE^sub 2^, EP1-R-EP4-R and one type each for PGD^sub 2^, DP-R, and PGF^sub 2α^, FP-R. The mechanisms by which prostaglandins modulate the hepatocyte responding phenotype are poorly characterized. We have studied the concentration and time effect of PGE^sub 2^, PGD^sub 2^ and PGF^sub 2α^ on the mRNA expression level of their own receptors in the presence or absence of the inflammatory signal interleukin 6 (IL-6). The mRNA levels were determined in primary adult rat hepatocytes upon treatment with either prostaglandin (5 μM or 50 μM), or IL-6 (100 ng/ml), or both, for 4-24 h. A marked, concentration-dependent induction of EP2-R mRNA expression was promoted by PGE^sub 2^, PGD^sub 2^ or PGF^sub 2α^ after 4 h, whereas EP1-R, EP3-R and EP4-R transcript levels were unaffected. This expression pattern changed substantially upon 24 h. The induction of EP2-R mRNA, persisted, though attenuated. Furthermore, EP1-R mRNA upregulated two-three fold and EP3-R mRNA decreased modestly by 50 μM prostaglandin. None of the treatments affected the FP-R mRNA level, while that of DP-R mRNA was undetectable. In the presence of IL-6, prostaglandins had no such effects, but they did attenuate the IL-6-mediated changes in prostaglandin receptor mRNA expression. The findings indicate that prostaglandins modulate the prostaglandin receptor gene expression programme in primary adult rat hepatocytes in a manner that is specific to the receptor, the concentration and time of exposure, and the inflammatory condition of the cell (Mol Cell Biochem 266: 183-189, 2004)[PUBLICATION ABSTRACT]