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Differential modulation of prostaglandin receptor mRNA abundance by prostaglandins in primary cultured rat hepatocytes

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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 PGE2, EP1-R–EP4-R and one type each for PGD2, DP-R, and PGF2α, FP-R. The mechanisms by which prostaglandins modulate the hepatocyte responding phenotype are poorly characterized. We have studied the concentration and time effect of PGE2, PGD2 and PGF2α 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 PGE2, PGD2 or PGF2α 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)

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Authors and Affiliations

  1. Department of Physiology, University of the Basque Country Medical School, Bilbao, Spain

    Silvia Pérez, Eduardo N. Maldonado, Patricia Aspichueta, Begoña Ochoa & Yolanda Chico

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  1. Silvia Pérez
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  2. Eduardo N. Maldonado
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  3. Patricia Aspichueta
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  4. Begoña Ochoa
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  5. Yolanda Chico
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Pérez, S., Maldonado, E.N., Aspichueta, P. et al. Differential modulation of prostaglandin receptor mRNA abundance by prostaglandins in primary cultured rat hepatocytes. Mol Cell Biochem 266, 183–189 (2004). https://doi.org/10.1023/B:MCBI.0000049159.09349.02

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