@article{FennekohlSchieferdeckerJungermannetal.1999,
  author    = {Fennekohl, Alexandra and Schieferdecker, Henrike L. and Jungermann, Kurt and P{\"u}schel, Gerhard Paul},
  title     = {Differential expression of prostanoid receptors in hepatocytes, Kupffer cells, sinusoidal endothelial cells and stellate cells of rat liver},
  issn      = {0168-8278},
  year      = {1999},
  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 Gq-linked prostaglandin F2alpha receptor; they were devoid of any mRNA for the Gs-linked prostanoid receptors. Kupffer cells possessed the largest amount of mRNA for the Gs-linked prostaglandin E2 receptor subtype 2. Endothelial cells expressed high levels of mRNA for the Gq-linked thromboxane receptor and medium levels of mRNA for the Gs-linked prostacyclin receptor, while stellate cells had the highest levels of mRNA for the prostacyclin receptor. The mRNAs for the Gq-linked prostaglandin E2 receptor subtype 1 and the Gi-linked prostaglandin E2 receptor subtype 3 were expressed in hepatocytes and all nonparenchymal cell types at similar high levels, whereas the mRNA of the Gs-linked prostaglandin D2 receptor was expressed in all nonparenchymal cells at very low levels. CONCLUSIONS: In hepatocytes the prostaglandin F2alpha receptor can mediate an increase in glucose output via an increase of intracellular InsP3 while cAMP-dependent glucose output can be inhibited via the subtype 3 prostaglandin E2 receptor. The subtype 2 prostaglandin E2 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.},
  language  = {en}
}
@misc{GardemannPueschelJungermann1992,
  author    = {Gardemann, Andreas and P{\"u}schel, Gerhard Paul and Jungermann, Kurt},
  title     = {Nervous control of liver metabolism and hemodynamics},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-51346},
  year      = {1992},
  abstract  = {Content: Anatomy of hepatic innervation In vivo studies on the role of hepatic nerves Effects of hepatic nerves in isolated perfused liver Mechanism of action of sympathetic hepatic nerves},
  language  = {en}
}
@misc{PueschelJungermann1994,
  author    = {P{\"u}schel, Gerhard Paul and Jungermann, Kurt},
  title     = {Integration of function in the hepatic acinus : intercellular communication in neural and humoral control of liver metabolism},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-51279},
  year      = {1994},
  abstract  = {Content: Architecture of the liver acinus Functional zonation of the liver acinus Topological organization of metabollc regulation in the acinus Topological organization of defense and organ structure regulation in the acinus},
  language  = {de}
}
@misc{HespelingPueschelJungermannetal.1995,
  author    = {Hespeling, Ursula and P{\"u}schel, Gerhard Paul and Jungermann, Kurt and G{\"o}tze, Otto and Zwirner, J{\"o}rg},
  title     = {Stimulation of glycogen phosphorylase in rat hepatocytes via prostanoid release from Kupffer cells by recombinant rat anaphylatoxin C5a but not by native human C5a in hepatocyte/Kupffer cell co-cultures},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45909},
  year      = {1995},
  abstract  = {Human anaphylatoxin C3a had previously been shown to increase glycogenolysis in perfused rat liver and prostanoid formation in rat liver macrophages. Surprisingly, human C5a, which in other systems elicited stronger responses than C3a, did not increase glycogenolysis in perfused rat liver. Species incompatibilities within the experimental system had been supposed to be the reason. The current study supports this hypothesis: (1) In rat liver macrophages that had been maintained in primary culture for 72 h recombinant rat anaphylatoxin C5a in concentrations between 0.1 and 10 pg/ml increased the formation of thromboxane A₂, prostaglandin D₂, E₂ and F₂α6- to 12-fold over basal within 10 min. In contrast, human anaphylatoxin C5a did not increase prostanoid formation in rat Kupffer cells. (2) The increase in prostanoid formation by recombinant rat C5a was specific. It was inhibited by a neutralizing monoclonal antibody. (3) In co-cultures of rat hepatocytes and rat Kupffer cells but not in hepatocyte mono-cultures recombinant rat C5a increased glycogen phosphorylase activity 3-fold over basal. This effect was inhibited by incubation of the co-cultures with 500 μM acetylsalicyclic acid. Thus, C5a generated either locally in the liver or systemically e.g. in the course of sepsis, may increase hepatic glycogenolysis by a prostanoid-mediated intercellular communication between Kupffer cells and hepatocytes.},
  language  = {en}
}
@misc{MuscholPueschelHuelsmannetal.1991,
  author    = {Muschol, Waldemar and P{\"u}schel, Gerhard Paul and H{\"u}lsmann, Martina and Jungermann, Kurt},
  title     = {Eicosanoid-mediated increase in glucose and lactate output as well as decrease and redistribution of flow by complement-activated rat serum in perfused rat liver},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45892},
  year      = {1991},
  abstract  = {Rat serum, in which the complement sytem had been activated by incubation with zymosan, increased the glucose and lactate output, and reduced and redistributed the flow in isolated perfused rat liver clearly more than the control serum. Heat inactivation of the rat serum prior to zymosan incubation abolished this difference. Metabolic and hemodynamic alterations caused by the activated serum were dose dependent. They were almost completely inhibited by the cyclooxygenase inhibitor indomethacin and by the thromboxane antagonist 4-[2-(4-chlorobenzenesulfonamide)-ethyl]-benzene-acetica cid (BM 13505), but clearly less efficiently by the 5'-lipoxygenase inhibitor nordihydroguaiaretic acid and the leukotriene antagonist N-{3-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-propoxy]-4-chlorine-6-methyl-phenyl}-1H-tetrazole-5-carboxamide sodium salt (CGP 35949 B). Control serum and to a much larger extent complement-activated serum, caused an overflow of thromboxane B₂ and prostaglandin F₂α into the hepatic vein. It is concluded that the activated complement system of rat serum can influence liver metabolism and hemodynamics via release from nonparenchymal liver cells of thromboxane and prostaglandins, the latter of which can in turn act on the parenchymal cells.},
  language  = {en}
}
@misc{PueschelMiuraNeuschaeferRubeetal.1993,
  author    = {P{\"u}schel, Gerhard Paul and Miura, Hisayuki and Neusch{\"a}fer-Rube, Frank and Jungermann, Kurt},
  title     = {Inhibition by the protein kinase C activator 4β-phorbol 12-myristate 13-acetate of the prostaglandin F₂α-mediated and noradrenaline-mediated but not glucagon-mediated activation of glycogenolysis in rat liver},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45889},
  year      = {1993},
  abstract  = {In perfused rat livers, infusion of prostaglandin F₂α (PGF₂α) or noradrenaline increased glucose and lactate output and reduced flow. Glucagon increased glucose output and decreased lactate output without influence on flow. Infusion of phorbol 13-myristate 14-acetate (PMA) for 20 min prior to these stimuli strongly inhibited the metabolic and hemodynamic effects of noradrenaline, reduced the metabolic actions of PGF₂α but did not alter the effects of glucagon. In isolated rat hepatocytes PGF₂α, noradrenaline and glucagon activated glycogen phosphorylase but only PGF₂α and noradrenaline increased intracellular inositol 1,4,5-1risphosphalc (InsP₃). The noradrenaline- or PGF₂α-elicited activation of glycogen phosphorylase and increase in InsP₃ were largely reduced after preincubation of the cells for 10 min with PMA, whereas the glucagon-mediated enzyme activation was not affected. In contra\t to PMA, the phorbol ester 4a-phorbol 13,14-didecanoate. which does not activate protein kinase C, did not attenuate the PGF₂α- and noradrenaline-elicited stimulation of glucose output, glycogen phosphorylase and InsP, formation. Stimulation of InsP₃ formation by AlF₄⁻, which activates phospholipase C independently of the receptor, was not attenuated by prior incubation with PMA. Plasma membranes purified from isolated hepatocytes had both a high-capacity, low-affinity and a low-capacity, high-affinity binding site for PGF₂α. The Kd of the high-capacity, low-affinity binding site was close to the concentration of PGF₂α that increased glycogen phosphorylase activity halfmaximally. Binding to the high-capacity, low-affinity binding site was enhanced by guanosine 5'- 0-(3-thio)triphosphate (GTP[S]). This high-capacity, low-affinity site might thus represent the receptor. The Bmax and Kd of the high-capacity site, as well as the enhancement by GTP[S] of PGF₂α binding to this site, remained unaffected by PMA pretreatment. It is concluded that, in hepatocytes, activation of protein kinase C by PMA interrupted the InsP₃-mediated signal pathway from PGF₂α via a PGF₂α receptor and phospholipase C to glycogen phosphorylase at a point distal of the receptor prior to phospholipase C.},
  language  = {en}
}
@misc{NeuschaeferRubePueschelJungermann1993,
  author    = {Neusch{\"a}fer-Rube, Frank and P{\"u}schel, Gerhard Paul and Jungermann, Kurt},
  title     = {Characterization of prostaglandin-F₂α-binding sites on rat hepatocyte plasma membranes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45863},
  year      = {1993},
  abstract  = {Prostaglandin (PG)F₂α has previously been shown to increase glucose output from perfused livers and isolated hepatocytes, where it stimulated glycogen phosphorylase via an inositol-trisphosphatedependent signal pathway. In this study, PGF₂α binding sites on hepatocyte plasma membranes, that might represent the putative receptor, were characterized. Binding studies could not be performed with intact hepatocytes, because PGF₂α accumulated within the cells even at 4°C. The intracellular accumulation was an order of magnitude higher than binding to plasma membranes. Purified hepatocyte plasma membranes had a high-affinity/low-capacity and a low-affinity/highcapacity binding'site for PGF₂α. The respective binding constants for the high-affinity site were Kd = 3 nM and Bmax = 6 fmol/mg membrane protein, and for the low-affinity site Kd = 426 nM and Bmax = 245 fmol/mg membrane protein. Specific PGF₂α binding to the low-affinity site, but not to the high-affinity site, could be enhanced most potently by GTP[γS] followed by GDP[ϐS] and GTP, but not by ATP[γS] or GMP. PGF₂α competed most potently with [³H]PGF₂α for specific binding to hepatocyte plasma membranes, followed by PGD₂ and PGE₂. Since the low-affinity PGF₂α-binding site had a Kd in the concentration range in which PG had previously been shown to be half-maximally active, and since this binding site showed a sensitivity to GTP, it is concluded that it might represent the receptor involved in the PGF₂α signal chain in hepatocytes. A biological function of the high-affinity site is currently not known.},
  language  = {en}
}
@misc{PueschelKirchnerSchroederetal.1993,
  author    = {P{\"u}schel, Gerhard Paul and Kirchner, C. and Schr{\"o}der, A. and Jungermann, Kurt},
  title     = {Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45853},
  year      = {1993},
  abstract  = {Prostaglandin E₂ has been reported both to stimulate glycogen-phosphorylase activity (glycogenolytic effect) and to inhibit the glucagon-stimulated glycogen-phosphorylase activity (antiglycogenolytic effect) in rat hepatocytes. It was the purpose of this study to resolve this apparent contradiction and to characterize the signalling pathways and receptor subtypes involved in the opposing prostaglandin E₂ actions. Prostaglandin E₂ (10 μM) increased glucose output, glycogen-phosphorylase activity and inositol trisphosphate formation in hepatocyte cell culture andor suspension. In the same systems, prostaglandin E₂ decreased the glucagon-stimulated (1 nM) glycogen-phosphorylase activity and cAMP formation. The signalling pathway leading to the glycogenolytic effect of PGE₂ was interrupted by incubation of the hepatocytes with 4P-phorbol 12-myristate 13-acetate (100 nM) for 10 min, while the antiglycogenolytic effect of prostaglandin E₂ was not attenuated. The signalling pathway leading to the antiglycogenolytic effect of prostaglandin E₂ was interrupted by an incubation of cultured hepatocytes with pertussis toxin (100 ng/ml) for 18 h, whereas the glycogenolytic effect of prostaglandin E₂ was enhanced. The EP₁/EP₃ prostaglandin-E₂-receptor-specific prostaglandin E₂ analogue Sulproston had a stronger glycogenolytic potency than the EP₃ prostaglandin-E₂-receptor-specific prostaglandin E₂ analogue Misoprostol. The antiglycogenolytic potency of both agonists was equal. It is concluded that the glycogenolytic and the antiglycogenolytic effects of prostaglandin E₂ are mediated via different signalling pathways in hepatocytes possibly involving EP₁ and EP₃ prostaglandin E₂ receptors, respectively.},
  language  = {en}
}
@misc{PueschelJungermann1988,
  author    = {P{\"u}schel, Gerhard Paul and Jungermann, Kurt},
  title     = {Activation of inositol phosphate formation by circulating noradrenaline but not by sympathetic nerve stimulation with a similar increase of glucose release in perfused rat liver},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45846},
  year      = {1988},
  abstract  = {In the isolated rat liver perfused in situ, stimulation of the nerve bundles around the hepatic artery and portal vein caused an increase of glucose and lactate output and a reduction of perfusion flow. These changes could be inhibited completely by α-receptor blockers. The possible involvement of inositol phosphates in the intracellular signal transmission was studied. 1. In cell-suspension experiments, which were performed as a positive control, noradrenaline caused an increase in glucose output and, in the presence of 10 mM LiCl, a dose-dependent and time-dependent increase of inositol mono, bis and trisphosphate. 2. In the perfused rat liver 1 μM noradrenaline caused an increase of glucose and lactate output and in the presence of 10 mM LiCl a time-dependent increase of inositol mono, bis and trisphosphate that was comparable to that observed in cell suspensions. 3. In the perfused rat liver stimulation of the nerve bundles around the portal vein and hepatic artery caused a similar increase in glucose and lactate output to that produced by noradrenaline, but in the presence of 10 mM LiCl there was a smaller increase of inositol monophosphate and no increase of inositol bis and trisphosphate. These findings are in line with the proposal that circulating noradrenaline reaches every hepatocyte, causing a clear overall increase of inositol phosphate formation and thus calcium release from the endoplasmic reticulum, while the hepatic nerves reach only a few cells causing there a small local change of inositol phosphate metabolism and thence a propagation of the signal via gap junctions.},
  language  = {en}
}
@misc{NeuschaeferRubeDeVriesHaeneckeetal.1994,
  author    = {Neusch{\"a}fer-Rube, Frank and DeVries, Christa and H{\"a}necke, Kristina and Jungermann, Kurt and P{\"u}schel, Gerhard Paul},
  title     = {Molecular cloning and expression of a prostaglandin E₂ receptor of the EP₃ϐ subtype from rat hepatocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45830},
  year      = {1994},
  abstract  = {Rat hepatocytes have previously been reported to possess prostaglandin E₂ receptors of the EP₃-type (EP₃-receptors) that inhibit glucagonstimulated glycogenolysis by decreasing cAMP. Here, the isolation of a functional EP₃ϐ receptor cDNA clone from a rat hepatocyte cDNA library is reported. This clone can be translated into a 362-amino-acid protein, that displays over 95\% homology to the EP₃ϐ receptor from mouse mastocytoma. The amino- and carboxy-terminal region of the protein are least conserved. Transiently transfected HEK 293 cells expressed a single binding site for PGE₂ with an apparent Kd of 15 nM. PGE₂ > PGF₂α > PGD₂ competed for [³H]PGE₂ binding sites as did the EP₃ receptor agonists M\&B 28767 = sulprostone > misoprostol but not the EP₁ receptor antagonist SC 19220. In stably transfected CHO cells M\&B 28767 > sulprostone = PGE₂ > misoprostol > PGF₂α inhibited the forskolin-elicited cAMP formation. Thus, the characteristics of the EP₃ϐ receptor of rat hepatocytes closely resemble those of the EP₃ϐ receptor of mouse mastocytoma.},
  language  = {en}
}