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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 36 (1981), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cholera toxin catalyzed the ADP-ribosylation of the pituitary protein hormones thyrotropin (TSH), lutropin (LH), follitropin (FSH), human chorionic gonadotropin (hCG). and corticotropin (ACTH)1–24, and ADP-ribosylation of the basic proteins histone subfraction H1 and protamine. Casein and phosvitin, acidic nuclear proteins, did not act as acceptors for toxin-catalyzed ADP-ribosylation. The isolated TSH A and B subunits were tested for their ADP-ribose acceptor activity. The TSH A subunit showed fourfold greater ADP-ribose acceptor activity than the TSH B subunit. The ADP-ribose acceptor protein protamine was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis following incubation with cholera toxin under ADP-ribosylating conditions. [3H]ADP-ribose incorporated into protein from [3H]NAD migrated with the acceptor protein protamine. In the absence of added acceptor protein, the [3H]ADP-ribose incorporated into protein migrated with the A1 fragment of cholera toxin. Cholera toxin A and B subunits were isolated and tested for their ability to catalyze the transfer of ADP-ribose to protamine. The cholera toxin A subunit showed 50-fold greater ADP-ribosyltransferase activity than the B subunit. Our data indicate that a variety of adenohypophyseal hormones and regulatory proteins act as acceptors for toxin-catalyzed ADP-ribosylation. These studies may help in understanding the role of endogenous ADP-ribosyltransferases and the physiological effects of this modification of protein.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 41 (1983), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The cerebellum of mouse appears to have only the adenosine A1 receptor, which decreases adenylate cyclase activity, and not the A2 receptor, which increases adenylate cyclase activity. The adenosine analog N6-(l-phenylisopropyl)adenosine (PIA), stimulates the Al receptor in a membrane preparation and decreases basal adenylate cyclase activity by 40%. The EC50 for PIA is approximately 50 nM. To associate the A1 receptor with a cerebellar cell type, three different neurological mutant mouse strains were studied: staggerer (Purkinje and granule cell defect), nervous (Purkinje cell defect), and weaver (granule cell defect). PIA was unable to effect a maximal decrease in adenylate cyclase activity of membranes prepared from cerebella of the staggerer and weaver mice in comparison with the respective littermate control mice. In contrast, membranes from nervous mice and their littermates showed similar PIA dose-response curves. Moreover, the diminished PIA response observed in the weaver cerebellum, when compared with the control littermate, was not detected in the striatum. This suggests no overall brain defect in the adenosine A1 receptors coupled to adenylate cyclase of the weaver mouse. We conclude that a loss of granule cells coincides with an attenuated response to PIA, implying that the A1 receptors are associated with the granule cells of the cerebellum.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We describe a rapid, sensitive method to determine brain adenosine content by HPLC. Adenosine is first reacted with chloroacetaldehyde to form fluorescent 1, N6-ethenoadenosine. The derivative is then separated from interfering compounds by HPLC on a C18 reverse-phase column and quantitated by fluorometry. We found that adenosine was rather uniformly distributed in nine brain regions of animals killed by microwave radiation. In contrast, there was an increase of adenosine in hippocampus, frontal cortex, and especially striatum of animals killed by decapitation. Moreover, adenosine content increased approximately 10-fold in the thalamus, mesencephalon, and pons-medulla if the animals were exposed to CO2 for 1 min before they were killed by microwave radiation. Our method should be a useful aid for providing new information about the metabolic and proposed transmitter roles of brain adenosine.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 51 (1988), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 30 mg/kg i.p. daily for 7 days, was administered to mice. This dosage regimen resulted in an ∼50% reduction of striatal dopamine (DA) level. Chronic administration of GM1 ganglioside (II3NeuAc-GgOse Cer), beginning between 1 to 4 days after terminating MPTP dosing, resulted in partial restoration of the striatal DA level. From dose- and time-response studies, it appeared that 30 mg/kg i.p. of GM1 administered daily for ∼23 days resulted in an ∼80% restoration of the DA level and complete restoration of the 3,4-dihydroxyphenylacetic acid (DOPAC) content. This dosage of GM1 also restored the turnover rate of DA in the striatum to near normal. Discontinuing GM1 treatment resulted in a fall of DA and DOPAC levels to values found in mice treated with MPTP alone. There was no evidence for regeneration of nerve terminal amine reuptake in the GM1-treated mice as evaluated by DA uptake into synaptosomes. Our biochemical findings in animals suggest that early GM1 ganglioside treatment of individuals with degenerative diseases of dopaminergic nigrostriatal neurons might be fruitful.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathology and clinical symptoms that resemble Parkinsonism in primates and humans. In mice it induces a long-lasting depletion of neostriatal 3,4-dihydroxyphenylethylamine (dopamine) content. Using the mouse, we found that MPTP induces a fall of dopamine and a rise of acetylcholine in the neostriatum. Both responses to MPTP can be blocked by prior treatment with atropine or trihexyphenidyl.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 43 (1984), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: An existing method for measuring acetylcholine (ACh) and choline (Ch) is shown to be useful formeasuring the turnover rate of ACh in mouse brain. Methl-[3H]Ch is injected into mice. They are killed atdifferent times by microwave irradiation and Ch and AChextracted and separated by reverse-phase HPLC. Ch andACh are converted to hydrogen peroxide by a post-column enzyme reaction. Hydrogen peroxide, which isdirectly related to the tissue content of Ch or ACh, isdetermined electrochemically. The fractions that corre-spond to the detector response for Ch and ACh are col-lected for the measurement of radioactivity. In this wayspecific radioactivities of endogenous Ch and ACh areestimated in the same sample. We used the specific ra-dioactivity values determined by this procedure to esti-mate the turnover of ACh for striatum, cerebral cortex, and hippocampus of the mouse.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Chronic inhibition of acetylcholinesterase activity by treatment with diisopropylfluorophosphate (DFP) decreased the capacity of acetylcholine (ACh) acting at a muscarinic receptor to inhibit basal adenylate cyclase activity in homogenates from rat striatum. There was also a loss of the capacity of ACh to inhibit the activation of adenylate cyclase by dopamine. The desensitization of the muscarinic receptor adenylate cyclase complex was associated with a marked attenuation of the capacity of ACh to stimulate a high-affinity GTPase activity present in striatal membranes. The EC50 value of ACh for inhibiting adenylate cyclase and for stimulating GTPase activity increased following treatment with DFP, while the Hill coefficient for both responses was unaltered.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Tyrosine hydroxylase in rat retina is activated in vivo as a consequence of photic stimulation. Tyrosine hydroxylase in crude extracts of dark-adapted retinas is activated in vitro by incubation under conditions that stimulate protein phosphorylation by cyclic AMP-dependent protein kinase. Comparison of the activations of the enzyme by photic stimulation in vivo and protein phosphorylation in vitro demonstrated several similarities. Both treatments decreased the apparent Km of the enzyme for the synthetic pterin cofactor 6MPH4. Both treatments also produced the same change in the relationships of tyrosine hydroxylase activity to assay pH. When retinal extracts containing tyrosine hydroxylase activated either in vivo by photic stimulation or in vitro by protein phosphorylation were incubated at 25°C, the enzyme was inactivated in a time-dependent manner. The inactivation of the enzyme following both activation in vivo and activation in vitro was partially inhibited by sodium pyrophosphate, an inhibitor of phosphoprotein phosphatase. In addition to these similarities, the activation of tyrosine hydroxylase in vivo by photic stimulation was not additive to the activation in vitro by protein phosphorylation. These data indicate that the mechanism for the activation of tyrosine hydroxylase that occurs as a consequence of light-induced increases of neuronal activity is similar to the mechanism for activation of the enzyme in vitro by protein phosphorylation. This observation suggests that the activation of retinal tyrosine hydroxylase in vivo may be mediated by phosphorylation of tyrosine hydroxylase or some effector molecule associated with the enzyme.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dopamine receptor adenylate cyclase complex of a rat striatal membrane preparation became more responsive to dopamine following the injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle or following the subcutaneous implantation of morphine pellets. Moreover, the membrane cyclase system was more responsive to activation by GTP, guanyl-5′-yl-imidodiphosphate and Mn-ATP. These observations suggest that both 6-OHDA and morphine induce similar biochemical changes in striatum and that the increased responsiveness arises, in part, from modification of the nucleotide regulatory and/or catalytic components of adenylate cyclase.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Xenograft ; Fetal pig ; Rat striatum ; Rotational behavior ; Tyrosine hydroxylase immunohistochemistry ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A suspension of cells from embryonic day 21 fetal pig ventral mesencephalon was transplanted into the striatum of 20 immunosuppressed rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Of these rats, 15 showed reduction of amphetamine-induced ipsilateral rotation by 9 weeks and complete reversal of rotation by 14–17 weeks. Animals maintained stable reversal of rotations (contralateral direction) until cessation of Cyclosporin A (CyA) treatment at 15–20 weeks. Within 4–9 weeks after CyA removal, these rats showed exclusively ipsilateral rotations during behavioral testing which were comparable to pre-transplant levels, suggesting that the grafts were rejected upon cessation of CyA treatment. Rats were sacrificed and tyrosine hydroxylase (TH) immunohistochemistry was performed at several time points, both on and off CyA, to examine a possible correlation between the degree of rotational behavior and the number of TH- positive surviving grafted cells. Staining showed large numbers (230–12,329) of TH-positive surviving cells in animals displaying a high degree of rotational correction (1.6 to -9.6 net ipsilateral rotations/min) after cessation of CyA treatment. Two control groups, those transplanted with nonneuronal cells from the pig ventral mesencephalon (n=5) and those receiving only daily CyA injections (n=4) showed no significant reduction of net ipsilateral rotations throughout the experiment. No TH-positive surviving cells were seen in the one non-neuronal transplant analyzed. This data demonstrates long-term retention of xenografted tissue with immunosuppression and its concomitant restoration of normal motor behavior in the rat model of Parkinson's disease.
    Type of Medium: Electronic Resource
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