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Konrad Löffelholz - One of the best experts on this subject based on the ideXlab platform.

  • ACETYLCholine RELEASE AND Choline AVAILABILITY IN RAT HIPPOCAMPUS : EFFECTS OF EXOGENOUS Choline AND NICOTINAMIDE
    The Journal of pharmacology and experimental therapeutics, 1997
    Co-Authors: Andrea Köppen, Jochen Klein, Christina Erb, Konrad Löffelholz
    Abstract:

    The influence of Choline availability on acetylCholine (ACh) release in the hippocampus of the awake rat was investigated using the microdialysis procedure. Three treatments enhancing Choline availability for basal and atropine-evoked ACh release were evaluated: acute administration of Choline chloride (20 mg/kg i.p.); pretreatment of animals with nicotinamide (10 mmol/kg s.c.) 2 hr before atropine injection and dietary Choline supplementation (5-fold increase of Choline intake for 15–18 days). Although acute Choline administration led to a short-lasting (15 min) increase of basal Choline efflux by 25% and nicotinamide caused a long-lasting (5 hr) increase by 105%, neither one affected basal ACh release. However, basal release of Choline (1.38 pmol/min) and of ACh (114 fmol/min) in the hippocampus was slightly increased in Choline-supplemented animals (Choline: 1.92 pmol/min; ACh: 140 fmol/min). In untreated animals, atropine administration caused a 3-fold increase of ACh efflux that lasted approximately 2.5 hr. All treatments, acute or chronic Choline and nicotinamide, led to significant increases of the maximum and duration of atropine-evoked ACh release. Total atropine-evoked ACh efflux (area under the curve) was increased 2- to 3-fold, with the largest effect evoked by the combination of nicotinamide and Choline. The results clearly demonstrate that, under stimulated conditions, hippocampal ACh release could be facilitated when the availability of Choline for ACh synthesis was enhanced by dietary or pharmacological means. Under certain conditions, significant effects of increased Choline availability on ACh release can be revealed in the absence of an overall increase of extracellular Choline.

  • Synergistic effect of nicotinamide and Choline administration on extracellular Choline levels in the brain.
    The Journal of pharmacology and experimental therapeutics, 1993
    Co-Authors: Andrea Köppen, Jochen Klein, T Holler, Konrad Löffelholz
    Abstract:

    Experimental studies indicate that the availability of free Choline is a rate-limiting step for acetylCholine synthesis in central Cholinergic neurons, especially when the release of acetylCholine is increased. In the present study we applied the microdialysis technique to measure the concentration of extracellular Choline in the rat hippocampus. The i.p. injection of 6, 20 and 60 mg/kg of Choline chloride led to short-lasting elevations of the basal Choline efflux (1.78 pmol/min) by 14, 26 and 131%. N-Methylnicotinamide, a metabolite of nicotinamide, has been reported to inhibit the outward transport of Choline from the cerebrospinal fluid to the blood. The s.c. injection of 5 and 10 mmol/kg of nicotinamide caused increases of extracellular Choline by 54 and 113%, respectively, and Choline levels remained elevated for several hr. Moreover, the administration of 10 mmol/kg of nicotinamide dramatically potentiated the effects of exogenous Choline administration on Choline availability in the central nervous system. The effects of 6 and 20 mg/kg of Choline chloride were increased by a factor of more than 10-fold when determined as area under the curve. Additional experiments demonstrated that neither nicotinamide nor N-methylnicotinamide (100 microM) have an influence on the uptake, metabolism or release of Choline in the hippocampal slice preparation. It is likely, therefore, that nicotinamide, after metabolic conversion in the brain to N-methylnicotinamide, leads to a blockade of Choline clearance from the brain. The combined administration of Choline and of a Choline transport blocker analogous to nicotinamide may be of potential use in central Cholinergic dysfunction.

  • Uptake and Metabolism of Choline by Rat Brain After Acute Choline Administration
    Journal of neurochemistry, 1992
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz, Jorg Schmitthenner
    Abstract:

    The present study is concerned with the uptake and metabolism of Choline by the rat brain. Intraperitoneal administration of Choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma Choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of Choline across the brain to positive values at plasma Choline levels of greater than 23 microM. Net Choline release and uptake were linearly dependent on the plasma Choline level in the physiological range of 10-50 microM, whereas the CSF Choline level was significantly increased only at plasma Choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]Choline chloride caused the net uptake of greater than 500 nmol/g of Choline by the brain as calculated from the AVD, which was reflected in a minor increase of free Choline level and a long-lasting increase of brain phosphorylCholine content, which paralleled the uptake curve. Loss of label from phosphorylCholine 30 min to 24 h after Choline administration was accompanied by an increase of label in phosphatidylCholine, an indication of a delayed transfer of newly taken-up Choline into membrane Choline pools. In conclusion, homeostasis of brain Choline is maintained by a complex system that interrelates Choline net movements into and out of the brain and Choline incorporation into and release from phospholipids.

  • Uptake and Storage of Choline by Rat Brain: Influence of Dietary Choline Supplementation
    Journal of neurochemistry, 1991
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz
    Abstract:

    In order to elucidate the regulation of the levels of free Choline in the brain, we investigated the influence of chronic and acute Choline administration on Choline levels in blood, CSF, and brain of the rat and on net movements of Choline into and out of the brain as calculated from the arteriovenous differences of Choline across the brain. Dietary Choline supplementation led to an increase in plasma Choline levels of 50% and to an increase in the net release of Choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the Choline concentration in the CSF and brain tissue was doubled. In the same rats, the injection of 60 mg/kg Choline chloride did not lead to an additional increase of the brain Choline levels, whereas in control animals Choline injection caused a significant increase; however, this increase in no case surpassed the levels caused by chronic Choline supplementation. The net uptake of Choline after acute Choline administration was strongly reduced in the high-Choline group (from 418 to 158 nmol/g). Both diet groups metabolized the bulk (greater than 96%) of newly taken up Choline rapidly. The results indicate that Choline supplementation markedly attenuates the rise of free Choline in the brain that is observed after acute Choline administration. The rapid metabolic Choline clearance was not reduced by dietary Choline load. We conclude that the brain is protected from excess Choline by rapid metabolism, as well as by adaptive, diet-induced changes of the net uptake and release of Choline.

Jochen Klein - One of the best experts on this subject based on the ideXlab platform.

  • ACETYLCholine RELEASE AND Choline AVAILABILITY IN RAT HIPPOCAMPUS : EFFECTS OF EXOGENOUS Choline AND NICOTINAMIDE
    The Journal of pharmacology and experimental therapeutics, 1997
    Co-Authors: Andrea Köppen, Jochen Klein, Christina Erb, Konrad Löffelholz
    Abstract:

    The influence of Choline availability on acetylCholine (ACh) release in the hippocampus of the awake rat was investigated using the microdialysis procedure. Three treatments enhancing Choline availability for basal and atropine-evoked ACh release were evaluated: acute administration of Choline chloride (20 mg/kg i.p.); pretreatment of animals with nicotinamide (10 mmol/kg s.c.) 2 hr before atropine injection and dietary Choline supplementation (5-fold increase of Choline intake for 15–18 days). Although acute Choline administration led to a short-lasting (15 min) increase of basal Choline efflux by 25% and nicotinamide caused a long-lasting (5 hr) increase by 105%, neither one affected basal ACh release. However, basal release of Choline (1.38 pmol/min) and of ACh (114 fmol/min) in the hippocampus was slightly increased in Choline-supplemented animals (Choline: 1.92 pmol/min; ACh: 140 fmol/min). In untreated animals, atropine administration caused a 3-fold increase of ACh efflux that lasted approximately 2.5 hr. All treatments, acute or chronic Choline and nicotinamide, led to significant increases of the maximum and duration of atropine-evoked ACh release. Total atropine-evoked ACh efflux (area under the curve) was increased 2- to 3-fold, with the largest effect evoked by the combination of nicotinamide and Choline. The results clearly demonstrate that, under stimulated conditions, hippocampal ACh release could be facilitated when the availability of Choline for ACh synthesis was enhanced by dietary or pharmacological means. Under certain conditions, significant effects of increased Choline availability on ACh release can be revealed in the absence of an overall increase of extracellular Choline.

  • Synergistic effect of nicotinamide and Choline administration on extracellular Choline levels in the brain.
    The Journal of pharmacology and experimental therapeutics, 1993
    Co-Authors: Andrea Köppen, Jochen Klein, T Holler, Konrad Löffelholz
    Abstract:

    Experimental studies indicate that the availability of free Choline is a rate-limiting step for acetylCholine synthesis in central Cholinergic neurons, especially when the release of acetylCholine is increased. In the present study we applied the microdialysis technique to measure the concentration of extracellular Choline in the rat hippocampus. The i.p. injection of 6, 20 and 60 mg/kg of Choline chloride led to short-lasting elevations of the basal Choline efflux (1.78 pmol/min) by 14, 26 and 131%. N-Methylnicotinamide, a metabolite of nicotinamide, has been reported to inhibit the outward transport of Choline from the cerebrospinal fluid to the blood. The s.c. injection of 5 and 10 mmol/kg of nicotinamide caused increases of extracellular Choline by 54 and 113%, respectively, and Choline levels remained elevated for several hr. Moreover, the administration of 10 mmol/kg of nicotinamide dramatically potentiated the effects of exogenous Choline administration on Choline availability in the central nervous system. The effects of 6 and 20 mg/kg of Choline chloride were increased by a factor of more than 10-fold when determined as area under the curve. Additional experiments demonstrated that neither nicotinamide nor N-methylnicotinamide (100 microM) have an influence on the uptake, metabolism or release of Choline in the hippocampal slice preparation. It is likely, therefore, that nicotinamide, after metabolic conversion in the brain to N-methylnicotinamide, leads to a blockade of Choline clearance from the brain. The combined administration of Choline and of a Choline transport blocker analogous to nicotinamide may be of potential use in central Cholinergic dysfunction.

  • Uptake and Metabolism of Choline by Rat Brain After Acute Choline Administration
    Journal of neurochemistry, 1992
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz, Jorg Schmitthenner
    Abstract:

    The present study is concerned with the uptake and metabolism of Choline by the rat brain. Intraperitoneal administration of Choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma Choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of Choline across the brain to positive values at plasma Choline levels of greater than 23 microM. Net Choline release and uptake were linearly dependent on the plasma Choline level in the physiological range of 10-50 microM, whereas the CSF Choline level was significantly increased only at plasma Choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]Choline chloride caused the net uptake of greater than 500 nmol/g of Choline by the brain as calculated from the AVD, which was reflected in a minor increase of free Choline level and a long-lasting increase of brain phosphorylCholine content, which paralleled the uptake curve. Loss of label from phosphorylCholine 30 min to 24 h after Choline administration was accompanied by an increase of label in phosphatidylCholine, an indication of a delayed transfer of newly taken-up Choline into membrane Choline pools. In conclusion, homeostasis of brain Choline is maintained by a complex system that interrelates Choline net movements into and out of the brain and Choline incorporation into and release from phospholipids.

  • Uptake and Storage of Choline by Rat Brain: Influence of Dietary Choline Supplementation
    Journal of neurochemistry, 1991
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz
    Abstract:

    In order to elucidate the regulation of the levels of free Choline in the brain, we investigated the influence of chronic and acute Choline administration on Choline levels in blood, CSF, and brain of the rat and on net movements of Choline into and out of the brain as calculated from the arteriovenous differences of Choline across the brain. Dietary Choline supplementation led to an increase in plasma Choline levels of 50% and to an increase in the net release of Choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the Choline concentration in the CSF and brain tissue was doubled. In the same rats, the injection of 60 mg/kg Choline chloride did not lead to an additional increase of the brain Choline levels, whereas in control animals Choline injection caused a significant increase; however, this increase in no case surpassed the levels caused by chronic Choline supplementation. The net uptake of Choline after acute Choline administration was strongly reduced in the high-Choline group (from 418 to 158 nmol/g). Both diet groups metabolized the bulk (greater than 96%) of newly taken up Choline rapidly. The results indicate that Choline supplementation markedly attenuates the rise of free Choline in the brain that is observed after acute Choline administration. The rapid metabolic Choline clearance was not reduced by dietary Choline load. We conclude that the brain is protected from excess Choline by rapid metabolism, as well as by adaptive, diet-induced changes of the net uptake and release of Choline.

Andrea Köppen - One of the best experts on this subject based on the ideXlab platform.

  • ACETYLCholine RELEASE AND Choline AVAILABILITY IN RAT HIPPOCAMPUS : EFFECTS OF EXOGENOUS Choline AND NICOTINAMIDE
    The Journal of pharmacology and experimental therapeutics, 1997
    Co-Authors: Andrea Köppen, Jochen Klein, Christina Erb, Konrad Löffelholz
    Abstract:

    The influence of Choline availability on acetylCholine (ACh) release in the hippocampus of the awake rat was investigated using the microdialysis procedure. Three treatments enhancing Choline availability for basal and atropine-evoked ACh release were evaluated: acute administration of Choline chloride (20 mg/kg i.p.); pretreatment of animals with nicotinamide (10 mmol/kg s.c.) 2 hr before atropine injection and dietary Choline supplementation (5-fold increase of Choline intake for 15–18 days). Although acute Choline administration led to a short-lasting (15 min) increase of basal Choline efflux by 25% and nicotinamide caused a long-lasting (5 hr) increase by 105%, neither one affected basal ACh release. However, basal release of Choline (1.38 pmol/min) and of ACh (114 fmol/min) in the hippocampus was slightly increased in Choline-supplemented animals (Choline: 1.92 pmol/min; ACh: 140 fmol/min). In untreated animals, atropine administration caused a 3-fold increase of ACh efflux that lasted approximately 2.5 hr. All treatments, acute or chronic Choline and nicotinamide, led to significant increases of the maximum and duration of atropine-evoked ACh release. Total atropine-evoked ACh efflux (area under the curve) was increased 2- to 3-fold, with the largest effect evoked by the combination of nicotinamide and Choline. The results clearly demonstrate that, under stimulated conditions, hippocampal ACh release could be facilitated when the availability of Choline for ACh synthesis was enhanced by dietary or pharmacological means. Under certain conditions, significant effects of increased Choline availability on ACh release can be revealed in the absence of an overall increase of extracellular Choline.

  • Synergistic effect of nicotinamide and Choline administration on extracellular Choline levels in the brain.
    The Journal of pharmacology and experimental therapeutics, 1993
    Co-Authors: Andrea Köppen, Jochen Klein, T Holler, Konrad Löffelholz
    Abstract:

    Experimental studies indicate that the availability of free Choline is a rate-limiting step for acetylCholine synthesis in central Cholinergic neurons, especially when the release of acetylCholine is increased. In the present study we applied the microdialysis technique to measure the concentration of extracellular Choline in the rat hippocampus. The i.p. injection of 6, 20 and 60 mg/kg of Choline chloride led to short-lasting elevations of the basal Choline efflux (1.78 pmol/min) by 14, 26 and 131%. N-Methylnicotinamide, a metabolite of nicotinamide, has been reported to inhibit the outward transport of Choline from the cerebrospinal fluid to the blood. The s.c. injection of 5 and 10 mmol/kg of nicotinamide caused increases of extracellular Choline by 54 and 113%, respectively, and Choline levels remained elevated for several hr. Moreover, the administration of 10 mmol/kg of nicotinamide dramatically potentiated the effects of exogenous Choline administration on Choline availability in the central nervous system. The effects of 6 and 20 mg/kg of Choline chloride were increased by a factor of more than 10-fold when determined as area under the curve. Additional experiments demonstrated that neither nicotinamide nor N-methylnicotinamide (100 microM) have an influence on the uptake, metabolism or release of Choline in the hippocampal slice preparation. It is likely, therefore, that nicotinamide, after metabolic conversion in the brain to N-methylnicotinamide, leads to a blockade of Choline clearance from the brain. The combined administration of Choline and of a Choline transport blocker analogous to nicotinamide may be of potential use in central Cholinergic dysfunction.

  • Uptake and Metabolism of Choline by Rat Brain After Acute Choline Administration
    Journal of neurochemistry, 1992
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz, Jorg Schmitthenner
    Abstract:

    The present study is concerned with the uptake and metabolism of Choline by the rat brain. Intraperitoneal administration of Choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma Choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of Choline across the brain to positive values at plasma Choline levels of greater than 23 microM. Net Choline release and uptake were linearly dependent on the plasma Choline level in the physiological range of 10-50 microM, whereas the CSF Choline level was significantly increased only at plasma Choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]Choline chloride caused the net uptake of greater than 500 nmol/g of Choline by the brain as calculated from the AVD, which was reflected in a minor increase of free Choline level and a long-lasting increase of brain phosphorylCholine content, which paralleled the uptake curve. Loss of label from phosphorylCholine 30 min to 24 h after Choline administration was accompanied by an increase of label in phosphatidylCholine, an indication of a delayed transfer of newly taken-up Choline into membrane Choline pools. In conclusion, homeostasis of brain Choline is maintained by a complex system that interrelates Choline net movements into and out of the brain and Choline incorporation into and release from phospholipids.

  • Uptake and Storage of Choline by Rat Brain: Influence of Dietary Choline Supplementation
    Journal of neurochemistry, 1991
    Co-Authors: Jochen Klein, Andrea Köppen, Konrad Löffelholz
    Abstract:

    In order to elucidate the regulation of the levels of free Choline in the brain, we investigated the influence of chronic and acute Choline administration on Choline levels in blood, CSF, and brain of the rat and on net movements of Choline into and out of the brain as calculated from the arteriovenous differences of Choline across the brain. Dietary Choline supplementation led to an increase in plasma Choline levels of 50% and to an increase in the net release of Choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the Choline concentration in the CSF and brain tissue was doubled. In the same rats, the injection of 60 mg/kg Choline chloride did not lead to an additional increase of the brain Choline levels, whereas in control animals Choline injection caused a significant increase; however, this increase in no case surpassed the levels caused by chronic Choline supplementation. The net uptake of Choline after acute Choline administration was strongly reduced in the high-Choline group (from 418 to 158 nmol/g). Both diet groups metabolized the bulk (greater than 96%) of newly taken up Choline rapidly. The results indicate that Choline supplementation markedly attenuates the rise of free Choline in the brain that is observed after acute Choline administration. The rapid metabolic Choline clearance was not reduced by dietary Choline load. We conclude that the brain is protected from excess Choline by rapid metabolism, as well as by adaptive, diet-induced changes of the net uptake and release of Choline.

Richard J. Wurtman - One of the best experts on this subject based on the ideXlab platform.

  • plasma Choline concentration varies with different dietary levels of vitamins b 6 b 12 and folic acid in rats maintained on Choline adequate diets
    British Journal of Nutrition, 2012
    Co-Authors: Nick Van Wijk, Carol Watkins, Mark Bohlke, Timothy J Maher, Robert Johan Joseph Hageman, Patrick Joseph Gerardus Hendrikus Kamphuis, Laus M Broersen, Richard J. Wurtman
    Abstract:

    Choline is an important component of the human diet and is required for the endogenous synthesis of Choline-containing phospholipids, acetylCholine and betaine. Choline can also be synthesised de novo by the sequential methylation of phosphatidylethanolamine to phosphatidylCholine. Vitamins B6 ,B 12 and folate can enhance methylation capacity and therefore could influence Choline availability not only by increasing endogenous Choline synthesis but also by reducing Choline utilisation. In the present experiment, we determined whether combined supplementation of these B vitamins affects plasma Choline concentration in a rat model of mild B vitamin deficiency which shows moderate increases in plasma homocysteine. To this end, we measured plasma Choline and homocysteine concentrations in rats that had consumed a B vitamin-poor diet for 4 weeks after which they were either continued on the B vitamin-poor diet or switched to a B vitamin-enriched diet for another 4 weeks. Both diets contained recommended amounts of Choline. Rats receiving the B vitamin-enriched diet showed higher plasma Choline and lower plasma homocysteine concentrations as compared to rats that were continued on the B vitamin-poor diet. These data underline the interdependence between dietary B vitamins and plasma Choline concentration, possibly via the combined effects of the three B vitamins on methylation capacity.

  • interactions of 3 4 diaminopyridine and Choline in stimulating acetylCholine release and protecting membrane phospholipids
    Brain Research, 1991
    Co-Authors: Levent R Buyukuysal, Todd C Holmes, Richard J. Wurtman
    Abstract:

    Abstract We investigated the effects of 3,4-DAP on ACh release from rat striatal sliers superfused with or without Choline, at rest and during electrical stimulation. In a Choline-free medium, 3,4-DAP increased basal and stimulated ACh release while lowering the net efflux of Choline; thus while thesum of ACh plus Choline released remained constant, theratio of released ACh to that of Choline was increased. The drug failed to affect tissue ACh, Choline or membrane phospholipid levels (including those of phosphatidylCholine). In a Choline-containing medium, 3,4-DAP potentiated the enhancement by Choline of both basal and electrically stimulated ACh release. Electrical stimulation alone increased ACh release from the slices without altering Choline efflux or depleting tissue Choline or ACh stores; however, this treatment did deplete membranes of phosphatidylCholine and of other major phospholipids. Superfusion of the slices with 3,4-DAP protected the slices from stimulation-induced phospholipid depletion. Calcium-dependent activation of high-affinity Choline uptake may underlie the observed effects of 3,4-DAP.

Martin D. Brand - One of the best experts on this subject based on the ideXlab platform.

  • The Choline transporter is the major site of control of Choline oxidation in isolated rat liver mitochondria
    FEBS letters, 1993
    Co-Authors: Claude P. Kaplan, Richard K. Porter, Martin D. Brand
    Abstract:

    The degree of control exerted by the mitochondrial Choline transporter over the Choline oxidation pathway was measured in isolated rat liver mitochondria. Choline transporter activity was titrated with hemicholinium-3, a known competitive inhibitor of the transporter. It was shown that the rate of betaine efflux from mitochondria was an accurate measure of Choline oxidation. The relative rate of Choline oxidation was measured as a function of the relative degree of inhibition of the transporter. The resulting data gave a flux control coefficient over Choline oxidation of 0.9 for the Choline transporter. It is concluded that the Choline transporter is the major site for control of Choline oxidation in isolated rat liver mitochondria.