[PGE.sub.2] stimulates [O.sub.2] uptake in hepatic parenchymal cells: involvement of the cAMP-dependent protein kinase

Qu, Wei, Lee M. Graves, and Ronald G. Thurman. [PGE.sub.2] stimulates [O.sub.2] uptake in hepatic parenchymal cells: involvement of the cAMP-dependent protein kinase. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G1048-G1054, 1999.--The aim of this study was to determine which [PGE.sub.2] receptors and signal transduction pathways are responsible for the stimulation of oxygen uptake in liver. Hepatic parenchymal cells isolated from female Sprague-Dawley rats were incubated either with [PGE.sub.2], 17-phenyl-omega-trinor [PGE.sub.2] (an [EP.sub.1]-specific agonist), or 11-deoxy [PGE.sub.1] (an [EP.sub.2]/[EP.sub.4]-specific agonist), and oxygen consumption was measured. Both [PGE.sub.2] and 11-deoxy [PGE.sub.1] stimulated oxygen consumption. However, an [EP.sub.1] agonist was without effect. Although [PGE.sub.2] elevated intracellular calcium, this occurred at concentrations ~500-fold lower than that required to stimulate oxygen uptake. [PGE.sub.2]-stimulated increases in cAMP formation correlated well with the increase in oxygen consumption. Dibutyryl cAMP also increased oxygen consumption. Furthermore, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, a cell-permeable inhibitor of protein kinase A (PKA), reduced the stimulation of oxygen uptake by [PGE.sub.2]. Incubation of isolated parenchymal cell mitochondria with the purified catalytic subunit of PKA and ATP increased both state 3 rates of oxygen uptake and the respiratory control ratio by ~50%. Activation of these events was prevented by incubation with the PKA inhibitory peptide, PKI. These findings are consistent with the hypothesis that [PGE.sub.2] stimulates oxygen consumption via an [EP.sub.2] and/or [EP.sub.4] subclass of receptors through the actions of cAMP on a cAMP-dependent protein kinase. prostaglandin [E.sub.2]; protein kinase A; mitochondria