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  • 1
    Digitale Medien
    Digitale Medien
    Biochemical Responses Mediated by N-Methyl-d-Aspartate Receptors in Rat Cortical Slices Are Differentially Sensitive to Magnesium (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 58 (1992), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The effects of magnesium on the inhibition of phosphoinositide (PI) hydrolysis and the stimulation of [3H]norepinephrine release by N-methyl-d-aspartate (NMDA) in rat cortical slices were investigated. Removal of the magnesium from the buffer resulted in a small reduction of the inhibitory effect of 100 μM NMDA (34% inhibition in the absence of magnesium, compared with 51% for the control) when slices were coincubated with NMDA and carbachol. Addition of 10 mM Mg2+ also allowed the inhibitory effect of 100 μM NMDA on carbachol-stimulated PI hydrolysis to be expressed (44% inhibition) under these conditions. Concentration–effect curve analysis for the NMDA-induced inhibition of carbachol-stimulated PI hydrolysis indicated that the IC50 for NMDA was decreased from 14.9 μM for the control to 4.2 μM in the absence of magnesium. The absence of magnesium also had small effects on the concentration–effect curve for (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate reversal of the inhibitory effects of NMDA on carbachol-stimulated PI hydrolysis. The absence of magnesium also shifted slightly downward and flattened the NMDA concentration–effect curve if the cortical slices were pretreated with NMDA in the presence or absence of magnesium followed by removal of the NMDA and subsequent stimulation with carbachol. In contrast, cortical slices that had been prepared and treated similarly to the slices used in the PI experiments were very sensitive to the inhibitory effects of magnesium when using the NMDA stimulation of [3H]norepinephrine release assay in the presence or absence of carbachol. Thus, the modulation of PI hydrolysis by NMDA is much less sensitive to inhibition by magnesium than is the stimulation of neurotransmitter release. It is possible that NMDA receptors that mediate the inhibition of PI hydrolysis are coupled to ion channels that do not possess the characteristic voltage-dependent blockade by Mg2+.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb09758.x
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  • 2
    Digitale Medien
    Digitale Medien
    Ethanol Inhibition of N-Methyl-D-Aspartate-Stimulated Endogenous Dopamine Release from Rat Striatal Slices: Reversal by Glycine (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 54 (1990), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: N-Methyl-D-aspartate stimulated a concentration-dependent release of endogeneous dopamine from rat striatal slices. The threshold for activation was between 10 and 25 μM and reached a maximum at 1 mM. Release was completely blocked by magnesium or tetrodotoxin. Ethanol (10–200 mM) significantly inhibited the N-methyl-D-aspartate-stimulated release of dopamine by 20–45%, with half-maximal inhibition occurring at ∼21 mM. Addition of ethanol plus increasing concentrations of magnesium resulted in a greater inhibition of N-methyl-D-aspartate-stimulated dopamine release than that observed with magnesium alone. However, this effect appeared to be due to a noninteractive additive effect of the two antagonists, as the IC50 value for magnesium inhibition was not significantly altered by ethanol. Glycine, which had no effect on dopamine release by itself, completely reversed the inhibitory effects of ethanol (25 mM) at low micromolar concentrations. These results suggest that ethanol may produce its effects in striatal slices by interfering with a glycine modulatory site of the N-methyl-D-aspartate receptor-ionophore complex.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.1990.tb01931.x
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  • 3
    Digitale Medien
    Digitale Medien
    Differential Regulation of Phosphoinositide Phosphodiesterase Activity in Brain Membranes by Guanine Nucleotides and Calcium (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 50 (1988), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: We have shown previously that calcium and guanine nucleotides stimulate the activity of a phosphoinositide (PI) phosphodiesterase in membranes from rat cerebral cortex and that their effects are additive. To understand further guanine nucleotide- and calcium-stimulated PI phosphodiesterase activity, we have investigated the pH sensitivity and effects of inhibitors on the two modes of stimulation. NaF stimulates PI hydrolysis in brain membranes with an EC50 of 2 mM and a maximal effect at 10 mM, suggesting that a guanine nucleotide binding protein can regulate PI phosphodiesterase. Neomycin inhibited guanylylimidodiphosphate (GppNHp)-stimulated PI phosphodiesterase activity in a concentration-dependent manner, with 90% inhibition at 0.3 mM. Neomycin was not as effective at inhibiting calcium-dependent PI hydrolysis (32% inhibition at 0.3 mM). Chloroquine also had a greater inhibitory effect against GppNHp-stimulated PI phospho diesterase activity compared to calcium-dependent activity. Guanine nucleotide- and NaF-dependent activations of PI phosphodiesterase were strongly pH-dependent, with greatest stimulation observed at pH 5–6 and inhibition at more alkaline pH. Calcium-stimulated PI hydrolysis was not as sensitive to changes in pH and had a peak of activity at pH 9. Our findings of different pH optima and differential sensitivity to inhibitors suggest that calcium and guanine nucleotides may regulate PI phosphodiesterase in rat cortical membranes through independent mechanisms. Key Words: G-proteins—Calcium—Phosphoinositides—Membranes—Phosphoinositide phosphodiesterase—Brain. Gonzales R. A. and Crews F. T. Differential regulation of phosphoinositide phosphodiesterase activity in brain membranes by guanine nucleotides and calcium. J. Neurochem. 50, 1522–1528 (1988).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.1988.tb03039.x
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  • 4
    Digitale Medien
    Digitale Medien
    Variations in Membrane Sensitivity of Brain Region Synaptosomes to the Effects of Ethanol In Vitro and Chronic In Vivo Treatment (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 49 (1987), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: : The effects of chronic ethanol treatment on the membrane order of synaptosomes from the cerebral cortex, striatum, cerebellum, brainstem, and hippocampus of rats were determined by measuring the fluorescence polarization of diphenylhexatriene (DPH) that had been incorporated into the synaptosomal membranes. Fischer-344 rats either were fed a nutritionally complete ethanol-containing liquid diet for 5 months or pair-fed with a diet that contained sucrose substituted isocalorically for ethanol. Polarization values for synaptosomes from all the brain regions studied were similar except for those from cerebral cortical synaptosomal membranes, which were significantly less ordered. Ethanol in vitro (30–500 mM) decreased the polarization values in synaptosomes from sucrose-control rats for all brain regions, although the sensitivity of cerebellar synaptosomes to the membrane disordering effects of ethanol in vitro was significantly greater than that of synaptosomes from other brain regions. Chronic ethanol treatment did not alter baseline polarization for any brain region. Cerebellar and brainstem synaptosomes from the ethanol-fed rats were significantly less susceptible to the membrane disordering effects of ethanol in vitro compared to their sucrose controls, suggesting that chronic ethanol administration results in tolerance to ethanol's membrane effects. Striatal synaptosomes exhibited intermediate tolerance, whereas the sensitivities of cortical and hippocampal synaptosomes to membrane disordering by ethanol in vitro were not significantly affected by the chronic ethanol treatment. These results suggest that synaptosomal membranes have different membrane order requirements depending on the brain region from which they are prepared. Variations in brain regional neuronal membrane sensitivity to ethanol and differential tolerance development may contribute to some of the acute and chronic behavioral effects of ethanol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.1987.tb03408.x
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  • 5
    Digitale Medien
    Digitale Medien
    Cholinergic- and Adrenergic-Stimulated Inositide Hydrolysis in Brain: Interaction, Regional Distribution, and Coupling Mechanisms (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Carbachol and norepinephrine were used as agonists to compare and contrast cholinergic and adrenergic stimulation of inositide breakdown in rat brain slices. Carbachol acts through a muscarinic (possibly M1) receptor and norepinephrine acts through an α1 adrenoceptor. Studies in cerebral cortical slices indicated that both agonists stimulated the production of inositol-1- phosphate and glycerophosphoinositol. Although the initial rates for the stimulation of inositol phosphate release were similar for the two ligands, the response to norepinephrine continued for 60 min and was larger compared with carbachol which plateaued at 30 min. The presence of carbachol did not affect the ED50 for norepinephrine. Concentrations of carbachol near the ED50 in combination with norepinephrine resulted in an additive response whereas maximal concentrations of carbachol and norepinephrine resulted in a less than additive response in the cortex. This negative interaction was also seen in the hippocampus and hypothalamus but not in the striatum, brainstem, spinal cord, olfactory bulb, or cerebellum. Norepinephrine had a larger response than carbachol in the hippocampus, striatum, and spinal cord, but the reverse was true in the olfactory bulb. Manganese (1 mM) stimulated the incorporation of [3H]inositol into phosphatidylinositol (PtdIns) four- to fivefold but not into polyphosphoinositides. The stimulation by manganese of PtDIns labelling increased the monstimulated release of inositol phosphates but did not affect the stimulated release of inositol phosphates by carbachol or norepineph rine. These data suggest that: (a) there may be a common pool of inositides that can be hydrolyzed by cholinergic and/or adrenergic agonists in certain brain areas; (b) manganese may stimulate the labelling of a pool of PtdIns that does not interact with the receptor-coupled pool of inositides; and (c) there may be differences in the basic mechanisms coupling receptor occupation and inositide breakdown for cholinergic and adrenergic receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.1985.tb05526.x
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  • 6
    Digitale Medien
    Digitale Medien
    Quantification of Ethanol Concentrations in the Extracellular Fluid of the Rat Brain (2000)
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 75 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Traditional microdialysis techniques provide qualitative data, although quantitative data are often required for pharmacodynamic analyses. This study evaluated a potentially usefulin vivo delivery technique to calibrate microdialysis probes for ethanol. We measuredin vivo delivery extraction fractions within subjects across 2 days and found no change over time. We tested the effect of diffusion direction on extraction fraction and found that it was higher for ethanol diffusion out of the probe than for diffusion into the probe, bothin vitro andin vivo. Thein vivo extraction fraction ratio of diffusionIN versus diffusionOUT was 0.65 ± 0.03. Finally, we predicted extracellular brain ethanol concentrations after 1 g/kg ethanol administration usingin vivo delivery, “no net flux” dialysis, orin vivo delivery corrected for diffusion direction with thein vivo extraction fraction ratio. Bothin vivo delivery and “no net flux” dialysis predicted brain concentrations that were approximately one-third lower than blood concentrations, whereas the correctedin vivo delivery predicted extracellular concentrations very similar to blood concentrations. We conclude that microdialysis calibration methods for ethanol require a measure of extraction fraction for diffusion into the probe. Further studies are needed to establish whether this effect is common to other alcohols.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.0751685.x
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  • 7
    Digitale Medien
    Digitale Medien
    Effect of Ethanol on Extracellular Dopamine in Rat Striatum by Direct Perfusion with Microdialysis (1997)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 68 (1997), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The concentration-related effects of ethanol on extracellular dopamine (DA) in rat striatum were studied by direct perfusion through microdialysis probes in freely moving rats. Two sets of three ethanol concentrations were separately tested using a Latin square experimental design. Potassium stimulation with high potassium (50 mM) in artificial CSF (ACSF) preceding ethanol treatment confirmed the neuronal function of dopaminergic cells by increasing DA concentrations to 200–1,500% of basal levels. The perfusion with calcium-free ACSF applied at the end of each experiment confirmed the calcium dependency of the basal levels of extracellular DA by decreasing basal DA levels by 70%. The striatal volume measurement to examine the possible brain damage by direct ethanol perfusion suggested that ethanol did not increase the damage caused by the probe implantation at any ethanol concentration tested in this study. The 30-min direct perfusion of 510 and 860 mM ethanol resulted in a significant concentration-related stimulatory effect on the extracellular DA concentration in rat striatum (510 mM, 29% increase, p 〈 0.05; 860 mM, 66% increase, p 〈 0.05). However, there was no significant effect of ethanol at low concentrations, ≤170 mM. Considering the effective ethanol concentration in tissue areas in which DA is sampled, the data suggest that concentrations of ethanol associated with moderate intoxication do not directly affect the extracellular concentration of DA in the striatum. Therefore, the systemic effects of ethanol on striatal DA found in previous studies may be caused by the interaction with sites other than the striatum.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1046/j.1471-4159.1997.68041527.x
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  • 8
    Digitale Medien
    Digitale Medien
    Effect of operant self-administration of 10% ethanol plus 10% sucrose on dopamine and ethanol concentrations in the nucleus accumbens (2005)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 93 (2005), S. 0 
    Details
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Although operant ethanol self-administration can increase accumbal dopamine activity, the relationship between dopamine and ethanol levels during consumption remains unclear. We trained Long-Evans rats to self-administer escalating concentrations of ethanol (with 10% sucrose) over 7 days, during which two to four lever presses resulted in 20 min of access to the solution with no further response requirements. Accumbal microdialysis was performed in rats self-administering 10% ethanol (plus 10% sucrose) or 10% sucrose alone. Most ethanol (1.6 ± 0.2 g/kg) and sucrose intake occurred during the first 10 min of access. Sucrose ingestion did not induce significant changes in dopamine concentrations. Dopamine levels increased within the first 5 min of ethanol availability followed by a return to baseline, whereas brain ethanol levels reached peak concentration more than 40 min later. We found significant correlations between intake and dopamine concentration during the initial 10 min of consumption. Furthermore, ethanol-conditioned rats consuming 10% sucrose showed no effect of ethanol expectation on dopamine activity. The transient rise in dopamine during ethanol ingestion suggests that the dopamine response was not solely due to the pharmacological properties of ethanol. The dopamine response may be related to the stimulus properties of ethanol presentation, which were strongest during consumption.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1471-4159.2005.03137.x
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  • 9
    Digitale Medien
    Digitale Medien
    Receptors for phorbol esters are primarily localized in neurons: Comparison of neuronal and glial cultures (1988)
    Springer
    Neurochemical research 13 (1988), S. 51-56 
    Details
    ISSN: 1573-6903
    Schlagwort(e): Neuronal cultures ; glial cultures ; protein kinase C ; phorbol ester receptor ; spontaneously hypertensive rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Binding of [3H]PDB has been measured in the present study to determine the levels of protein kinase C in the neuronal and astrocytic glial cells in culture from rat brain. Binding of [3H]PDB to homogenates of cultured neuronal cells from the brains of normotensive and hypertensive rats was time-dependent and specific. The relative potency for competition by various phorbol esters to [3H]PDB binding was TPA 〉 β-PDD 〉 POE 〉 α-PDD ≥4αphorbol. Scatchard analysis showed that neuronal cultures from normotensive rat brains contained 2–3 fold more phorbol ester receptors compared with the glial cultures from the same brains. No differences in theK d andB max were observed between neuronal cultures from normotensive and spontaneously hypertensive rat brains. These studies suggest that the phorbol ester receptors are primarily localized in neuronal cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00971854
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  • 10
    Digitale Medien
    Digitale Medien
    Calcium channel involvement in potassium depolarization-induced phosphoinositide hydrolysis in rat cortical slices (1989)
    Springer
    Neurochemical research 14 (1989), S. 1067-1074 
    Details
    ISSN: 1573-6903
    Schlagwort(e): Calcium ; phosphoinositides ; brain slices ; inositol phosphates ; calcium agonists ; depolarization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The stimulation of production of inositol phosphates in rat cortical slices by KCl depolarization and the effects of calcium channel active drugs were investigated. Elevation of K+ in the medium up to 48 mM KCl caused a linear concentration-dependent increase in [3H]inositol phosphate accumulation. The KCl stimulated response was not significantly inhibited in the presence of muscarinic or α1-adrenergic antagonists. KCl stimulated the production of inositol trisphosphate at 60 min but not 10 min. Addition of peptidase inhibitors did not significantly affect KCl-stimulated PI hydrolysis. The KCl-stimulated response was still observed in the absence of extracellular calcium, although the net accumulation of inositol phosphates was greater in the presence of 0.1 or 0.5 mM calcium. KCl (48 mM) inhibited [3H]inositol uptake into phospholipids of cortical slices. The dihydropyridine calcium channel agonist BAY K 8644 stimulated PI hydrolysis in cortical slices in a concentration dependent manner in the presence of 19 mM KCl. The BAY K 8644-stimulated PI response was partially inhibited by 1μM atropine but not by 1μM prazosin. Calcium channel blockers nitrendipine, verapamil, flunarizine, and nifedipine slightly inhibited the PI response stimulated by 19 mM KCl in the presence or absence of BAY K 8644. The effects of the calcium channel antagonists were attenuated in the presence of 1 μM atropine. The peptide calcium channel blocker ω-conotoxin did not affect KCl-stimulated PI hydrolysis. These results suggest that endogenous muscarinic or adrenergic neurotransmitters are not involved in KCl-stimulated PI hydrolysis in cortical slices. Although extracellular calcium is necessary for optimal KCl-stimulated PI hydrolysis, it is not required for the expression of the KCl-evoked response suggesting that depolarization is the primary trigger for this stimulant.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00965612
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