@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{HespelingJungermannPueschel1995,
  author    = {Hespeling, Ursula and Jungermann, Kurt and P{\"u}schel, Gerhard Paul},
  title     = {Feedback-inhibition of glucagon-stimulated glycogenolysis in hepatocyte/kupffer cell cocultures by glucagon-elicited prostaglandin production in kupffer cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-16697},
  year      = {1995},
  abstract  = {Prostaglandins, released from Kupffer cells, have been shown to mediate the increase in hepatic glycogenolysis by various stimuli such as zymosan, endotoxin, immune complexes, and anaphylotoxin C3a involving prostaglandin (PG) receptors coupled to phospholipase C via a G(0) protein. PGs also decreased glucagon-stimulated glycogenolysis in hepatocytes by a different signal chain involving PGE(2) receptors coupled to adenylate cyclase via a G(i) protein (EP(3) receptors). The source of the prostaglandins for this latter glucagon-antagonistic action is so far unknown. This study provides evidence that Kupffer cells may be one source: in Kupffer cells, maintained in primary culture for 72 hours, glucagon (0.1 to 10 nmol/ L) increased PGE(2), PGF(2 alpha), and PGD(2) synthesis rapidly and transiently. Maximal prostaglandin concentrations were reached after 5 minutes. Glucagon (1 nmol/L) elevated the cyclic adenosine monophosphate (cAMP) and inositol triphosphate (InsP(3)) levels in Kupffer cells about fivefold and twofold, respectively. The increase in glyco gen phosphorylase activity elicited by 1 nmol/L glucagon was about twice as large in monocultures of hepatocytes than in cocultures of hepatocytes and Kupffer cells with the same hepatocyte density. Treatment of cocultures with 500 mu mol/L acetylsalicylic acid (ASA) to irreversibly inhibit cyclooxygenase (PGH-synthase) 30 minutes before addition of glucagon abolished this difference. These data support the hypothesis that PGs produced by Kupffer cells in response to glucagon might participate in a feedback loop inhibiting glucagon-stimulated glycogenolysis in hepatocytes.},
  language  = {en}
}
@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{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}
}
@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{PueschelChrist1994,
  author    = {P{\"u}schel, Gerhard Paul and Christ, Bruno},
  title     = {Inhibition by PGE₂ of glucagon-induced increase in phosphoenolpyruvate carboxykinase mRNA and acceleration of mRNA degradation in cultured rat hepatocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45792},
  year      = {1994},
  abstract  = {In cultured rat hepatocytes the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) is known to be induced by glucagon via an elevation of cAMP. Prostaglandin E₂ has been shown to antagonize the glucagon-activated cAMP formation, glycogen phosphorylase activity and glucose output in hepatocytes. It was the purpose of the current investigation to study the potential of PGE₂ to inhibit the glucagon-induced expression of PCK on the level of mRNA and enzyme activity. PCK mRNA and enzyme activity were increased by 0.1 nM glucagon to a maximum after 2 h and 4 h, respectively. This increase was completely inhibited if 10 μM PGE2 was added concomitantly with glucagon. This inhibition by PGE₂ of glucagon-induced PCK activity was abolished by pertussis toxin treatment. When added at the maximum of PCK mRNA at 2 h, PGE₂ accelerated the decay of mRNA and reduced enzyme activity. This effect was not reversed by pertussis toxin treatment. Since in liver PGE₂ is derived from Kupffer cells, which play a key role in the local inflammatory response, the present data imply that during inflammation PGE₂ may reduce the hepatic gluconeogenic capacity via a Gᵢ-linked signal chain.},
  language  = {en}
}
@misc{PueschelHespelingOppermannetal.1993,
  author    = {P{\"u}schel, Gerhard Paul and Hespeling, Ursula and Oppermann, Martin and Dieter, Peter},
  title     = {Increase in prostanoid formation in rat liver macrophages (Kupffer cells) by human anaphylatoxin C3a},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-16716},
  year      = {1993},
  abstract  = {Human anaphylatoxin C3a increases glycogenolysis in perfused rat liver. This action is inhibited by prostanoid synthesis inhibitors and prostanoid antagonists. Because prostanoids but not anaphylatoxin C3a can increase glycogenolysis in hepatocytes, it has been proposed that prostanoid formation in nonparenchymal cells represents an important step in the C3a-dependent increase in hepatic glycogenolysis. This study shows that (a) human anaphylatoxin C3a (0.1 to 10 mug/ml) dose-dependently increased prostaglandin D2, thromboxane B, and prostaglandin F2alpha formation in rat liver macrophages (Kupffer cells); (b) the C3a-mediated increase in prostanoid formation was maximal after 2 min and showed tachyphylaxis; and (c) the C3a-elicited prostanoid formation could be inhibited specifically by preincubation of C3a with carboxypeptidase B to remove the essential C-terminal arginine or by preincubation of C3a with Fab fragments of a neutralizing monoclonal antibody. These data support the hypothesis that the C3a-dependent activation of hepatic glycogenolysis is mediated by way of a C3a-induced prostanoid production in Kupffer cells.},
  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{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}
}