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

Abstract

Background/Aims: Prostanoids produced by nonparenchymal cells modulate the function of parenchymal and nonparenchymal liver cells during homeostasis and inflammation via eight classes of prostanoid receptors coupled to different G-proteins. Prostanoid receptor expression in parenchymal and nonparenchymal cells was studied in order to get a better insight into the complex prostanoid-mediated intrahepatic signaling network. Methods: RNA was isolated from freshly purified parenchymal and nonparenchymal rat liver cells and the mRNA level of all eight prostanoid receptor classes was determined by newly developed semiquantitative reverse transcription-polymerase chain reaction protocols. Results: The mRNAs for the prostanoid receptors were differentially expressed. Hepatocytes were the only cell type which contained the mRNA of the G q-linked prostaglandin F 2α 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. Endothelial cells expressed high levels of mRNA for the G q-linked thromboxane receptor and medium levels of mRNA for the G s-linked prostacyclin receptor, while stellate cells had the highest levels of mRNA for the prostacyclin receptor. The mRNAs for the G q-linked prostaglandin E 2 receptor subtype 1 and the G i-linked prostaglandin E 2 receptor subtype 3 were expressed in hepatocytes and all nonparenchymal cell types atsimilar high levels, whereas the mRNA of the G s-linked prostaglandin D 2 receptor was expressed in all nonparenchymal cells at very low levels. Conclusions: In hepatocytes the prostaglandin F 2α receptor can mediate an increase in glucose output via an increase of intracellular InsP 3 while cAMP-dependent glucose output can be inhibited via the subtype 3 prostaglandin E 2 receptor. The subtype 2 prostaglandin E 2 receptor can restrain the inflammatory response of Kupffer cells via an increase in intracellular cAMP. The thromboxane receptor and the prostacyclin receptor in sinusoidal endothelial and the prostacyclin receptor in stellate cells may be involved in the regulation of sinusoidal blood flow and filtration.