Differential expression of prostanoid receptors in hepatocytes, Kupffer cells, sinusoidal endothelial cells and stellate cells of rat liver

Background/Aims: Prostanoids produced by nonparenchymal cells modulate the function of parenchymal and nonparenchymal liver cells during homeostasis a nd inflammation via eight classes of prostanoid receptors coupled to differ ent G-proteins, Prostanoid receptor expression in parenchymal and nonparenc hymal cells was studied in order to get a better insight into the complex p rostanoid-mediated intrahepatic signaling network. Methods: RNA was isolated from freshly purified parenchymal and nonparenchy mal rat liver cells and the mRNA level of all eight prostanoid receptor cla sses was determined by newly developed semiquantitative reverse transcripti on-polymerase chain reaction protocols. Results: The mRNAs for the prostanoid receptors were differentially express ed. Hepatocytes were the only cell type which contained the mRNA of the G(q )-linked prostaglandin F-2 alpha receptor; they were devoid of any mRNA for the G(s)-linked prostanoid receptors, Kupffer cells possessed the largest amount of mRNA for the G(s)-linked prostaglandin E-2 receptor subtype 2. En dothelial cells expressed high levels of mRNA for the G(q)-linked thromboxa ne receptor and medium levels of mRNA for the G(s)-linked prostacyclin rece ptor, while stellate cells had the highest levels of mRNA for the prostacyc lin receptor. The mRNAs for the G(q)-linked prostaglandin E-2 receptor subt ype 1 and the G(i)-linked prostaglandin E-2 receptor subtype 3 were express ed in hepatocytes and all nonparenchymal cell types at similar high levels, whereas the mRNA of the G(s)-linked prostaglandin D-2 receptor was express ed in all nonparenchymal cells at very low levels. Conclusions: In hepatocytes the prostaglandin F-2 alpha receptor can mediat e an increase in glucose output via an increase of intracellular InsP(3) wh ile cAMP-dependent glucose output can be inhibited via the subtype 3 prosta glandin E-2 receptor. The subtype 2 prostaglandin E-2 receptor can restrain the inflammatory response of Kupffer cells via an increase in intracellula r cAMP. The thromboxane receptor and the prostacyclin receptor in sinusoida l endothelial and the prostacyclin receptor in stellate cells may be involv ed in the regulation of sinusoidal blood flow and filtration.