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1. |
Opioid Receptors in Magnesium‐Digitonin‐Solubilized Rat Brain Membranes Are Tightly Coupled to a Pertussis Toxin‐Sensitive Guanine Nucleotide‐Binding Protein |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 0999-1009
Yung H. Wong,
Catherine D. Demoliou‐Mason,
Eric A. Barnard,
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摘要:
AbstractOpioid receptors solubilized in Mg2+‐digitonin (2%, wt/vol) from Mg2+‐pretreated rat brain membranes maintain, in addition to high‐affinity opioid agonist binding, the modulation by guanine nucleotides. One of the modes of expression of the latter property is an attenuation of agonist binding by guanine nucleotides in the presence of Na+. To investigate the molecular basis of this modulation and to identify the G protein(s) involved, the soluble receptors were [32P]ADP‐ribosylated by means ofBordetellapertussis toxin and subjected to molecular size exclusion chromatography. In addition, soluble extracts were chromatographed on lectin and hydrophobic affinity columns. The binding of35S‐ and3H‐labelled analogues of GTP was also monitored in the species separated. The oligomeric G protein‐coupled opioid receptors and the guanine nucleotide/pertussis toxin‐sensitive species showed similar chromatographic properties in all three systems. This indicates that the biochemically functional G protein‐opioid receptor complex formed in Mg2+‐pretreated membranes in the absence of an agonist is stable in digitonin solution and to chromatographic separation. Further analysis showed that the guanine nucleotide modulation of opioid receptors is via the pertussis toxin substrates with Mrof 41,000 and 39,000, which are identified as Giand Goα su
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01840.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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2. |
Interaction Between S‐100 Proteins and Steady‐State and Taxol‐Stabilized Microtubules In Vitro |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1010-1017
Rosario Donato,
Ileana Giambanco,
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摘要:
AbstractS‐100 proteins are a group of three 21‐kilodalton, acidic, Ca2+‐binding proteins of the “E‐F hand” type shown to regulate several cell activities, including microtubule (MT) assembly‐disassembly. We show here that S‐100 proteins interact with MTs assembled from either whole microtubule protein or purified tubulin, both in the absence and in the presence of the MT‐stabilizing drug taxol. Evidence for the binding of S‐100 to MTs comes from both kinetic (turbidi‐metric) and binding studies. Kinetically, S‐100 enhances the disassembly of steady‐state MTs in the presence of high concentrations of colchicine or vinblastine at 10 μM free Ca2+and disassembles taxol‐stabilized MTs at high Ca2+concentrations. Experiments performed using125I‐labeled S‐100 show that S‐100 binds Ca2+independently to a single set of sites on taxol‐stabilized MTs assembled from pure tubulin with an affinity of 6 X 10‐5Mand a stoichiometry of 0.15 mol of S‐100/mol of polymerized tubulin. Under certain conditions, S‐100 proteins also cosediment with MTs prepared by coassembly of S‐100 with MTs, probably in the form of an S‐100‐tubulin complex. Because S‐100 binds to MTs under conditions where this protein fraction does not produce observable effects on the kinetics of assembly‐disassembly, e.g., in the absence of Ca2+at pH 6.7, we conclude that the S‐100 binding to MTs does not affect the stability of MTs per se, but rather creat
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01841.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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3. |
Release of Endogenous Taurine and γ‐Aminobutyric Acid from Brain Slices from the Adult and Developing Mouse |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1018-1024
Simo S. Oja,
Pirjo Kontro,
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摘要:
Abstract:The spontaneous and potassium‐stimulated release of endogenous taurine and γ‐aminobutyric acid (GABA) from cerebral cortex and cerebellum slices from adult and developing mice was studied in a superfusion system. The spontaneous release of GABA was of the same magnitude in slices from adult and developing mice, but the spontaneous release of taurine was considerably greater in the adults. The potassium‐stimulated release of GABA from cerebral cortex slices was about five times greater in adult than in 3‐day‐old mice, but the potassium‐stimulated release of taurine was more than six times greater in 3‐day‐old than in adult mice. In cerebellar slices from 7‐day‐old mice, potassium stimulation also evoked a massive release of taurine, whereas the evoked release from slices from adult mice was rather negligible. Also in cerebellar slices the potassium‐stimulated release of GABA exhibited the opposite quantitative pattern. The stimulated release of both GABA and taurine was partially calcium dependent. The results suggest that taurine may be an important regulator of excitability i
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01842.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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4. |
Distribution and Pharmacological Properties of the GABAA/ Benzodiazepine/Chloride Ionophore Receptor Complex in the Brain of the FishAnguilla anguilla |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1025-1034
M. G. Corda,
B. Longoni,
A. Cau,
S. Paci,
S. Salvadori,
U. Laudani,
G. Biggio,
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摘要:
Abstract:In the present study, we characterized the distribution and the pharmacological properties of the different components of the GABAAreceptor complex in the brain of the eel (Anguilla anguilla). Benzodiazepine recognition sites labeled “in vitro” with [3H]flunitrazepam ([3H]FNT) were present in highest concentration in the optic lobe and in lowest concentration in the medulla oblongata and spinal cord. A similar distribution was observed in the density of γ‐ [3H]aminobutyric acid ([3H]GABA) binding sites. GABA increased the binding of [3H]FNT in a concentration‐dependent manner, with a maximal enhancement of 45% above the control value, and, vice versa, diazepam stimulated the binding of [3H]GABA to eel brain membrane preparations. The density of benzodiazepine and GABA recognition sites and their reciprocal regulation were similar to those observed in the rat brain. In contrast, the binding of the specific ligand for the CI‐ionophore, t‐[35S]butylbicyclophosphorothionate ([35S]TBPS), to eel brain membranes was lower than that found in the rat brain. In addition, [35S]TBPS binding in eel brain was less sensitive to the inhibitory effects of GABA and muscimol and much more sensitive to the stimulatory effect of bicuculline, when compared with [35S]TBPS binding in the rat brain. Moreover, the uptake of36Cl‐into eel brain membrane vesicles was only marginally stimulated by concentrations of GABA or muscimol that significantly enhanced the36Cl‐uptake into rat brain membrane vesicles. Finally, intravenous administration of the β‐carboline inverse agonist 6,γ‐dimethoxy‐4‐ethyl‐;β‐carboline‐3‐carboxylic acid methyl ester (20 mg/kg) and of the chloride channel blocker pen‐tylenetetrazole (80 mg/kg) produced convulsions in eels that were antagonized by diazepam at doses five to 20 times higher than those required to produce similar effects in rats. The results may indicate a different functional activity of the GABA‐coupled chloride ionophore in the fish bra
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01843.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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5. |
Lysosulfatide (Galactosylsphingosine‐3‐O‐Sulfate) from Metachromatic Leukodystrophy and Normal Human Brain |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1035-1041
Birgitta Rosengren,
Pam Fredman,
Jan‐Eric Mansson,
Lars Svennerholm,
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摘要:
AbstractThe glycosphingolipid pattern was examined in three cases of late infantile metachromatic leukodystrophy (MLD): one with a relatively short (2.5 years), one with a long (7.8 years), and one with a very long (13.2 years) survival time. All values were compared with those of age‐matched normal controls. The cerebroside concentration was reduced to 25, 12, and 4%, respectively, in the MLD white matter, whereas the sulfatide concentration was increased up to 200% of the control value. The yield of myelin was reduced to<15% in the early case and to<3 and 1%, respectively, in the two later cases. There was no sign of increased sulfatide proportion in the myelin. The ganglioside pattern was normal in cerebral gray matter, but in the white matter, contents of gangliosides of the lacto series were significantly increased, in particular, the ganglioside suggested by us as being characteristic of reactive astrocytosis. For the first time, lysosulfatide was identified in MLD and normal human brains by mass spectrometry and radioimmunoaffinity TLC using specific monoclonal antibody. Its quantity was found to be similar in normal and MLD brains. These findings support our postulation that the lysoglycosphingolipids are synthesized de novo from sphingosine and that they do not play a key role in pathogenetic mechanism
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01844.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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6. |
Effect of Lithium and of Other Drugs Used in the Treatment of Manic Illness on the Cation‐Transporting Properties of Na+, K+‐ATPase in Mouse Brain Synaptosomes |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1042-1049
A. J. Wood,
M. Elphick,
D. G. Grahame‐Smith,
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摘要:
AbstractWe have developed and used a novel technique to investigate the effects of lithium and other psychotropic drugs on the cation‐transporting properties of the sodium‐ and potassium‐activated ATPase enzyme (Na+, K+‐ATPase) in intact synaptosomes. Rubidium‐86 uptake into intact synaptosomes is an active process and is inhibited by ∼75% in the presence of the Na+, K+‐ATPase inhibitor acetylstrophanthidin. In vitro addition of lithium to synaptosomes prepared from untreated mice causes a progressive inhibition of acetylstrophanthidin‐sensitive86Rb uptake, but only at concentrations higher than the clinical therapeutic range. However, pretreatment of mice for 14 days in vivo with lithium, carbamazepine, and haloperidol, but not phenytoin, causes a significant stimulation of86Rb uptake into synaptosomes via
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01845.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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7. |
Targeting and Processing of Pro‐Opiomelanocortin in Neuronal Cell Lines |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1050-1057
Gilles Noël,
Lyze Zollinger,
France Laliberté,
Eric Rassart,
Philippe Crine,
Guy Boileau,
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摘要:
AbstractPro‐opiomelanocortin (POMC) is the precursor to several pituitary hormones including adrenocorticotropic hormone and β‐endorphin (β‐END). POMC is also expressed in the brain, predominantly in discrete neuronal cell populations of the hypothalamus. In the pituitary and brain, POMC undergoes tissue‐specific proteolysis to release different bioactive peptides. POMC processing in neuronal cell lines was studied after infection of PC 12 and Neuro2A cells with a recombinant retrovirus carrying the porcine POMC cDNA. Our results indicate that both cell lines synthesize and target POMC to the regulated secretory pathway. Only the Neuro2A cells, however, can achieve proteolytic processing of POMC. Chromatographic and immunological characterization of the POMC‐related material showed that β‐lipotropin (β‐LPH) and nonacetylated β‐END(1‐31) are major maturation products of POMC in these cells. Release of both β‐LPH and β‐END(1‐31) from infected Neuro2A cells can be stimulated by secretagogues in a calcium‐dependent manner. Taken together, our results suggest that the cellular machinery of Neuro2A cells can recognize a foreign prohormone, target it to neurosecretory vesicles, process it into biologically active peptides, and secrete it in a manner chara
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01846.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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8. |
Acidosis, Acetazolamide, and Amiloride: Effects on22Na Transfer Across the Blood‐Brain and Blood‐CSF Barriers |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1058-1063
Vincent A. Murphy,
Conrad E. Johanson,
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摘要:
AbstractSprague‐Dawley rats were given treatments, known to decrease22Na movement into choroid plexus and CSF, to investigate their effect on22Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of22Na uptake into parietal cortex, pons‐medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of22Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH.,C1 injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of22Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of22Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is<30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+movement only across the choroidal epithel
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01847.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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9. |
Effects of Picrotoxin Treatment on GABAAReceptor Supramolecular Complexes in Rat Brain |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1064-1070
Yoshihisa Ito,
Dong Koo Lim,
Toshitaka Nabeshima,
Ing K. Ho,
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摘要:
AbstractThe effects of acute and chronic administration of a subconvulsive dose of picrotoxin ont‐[35S]butylbieyclophosphorothionate ([35S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague‐Dawley rats were examined. Acute administration of a sub‐convulsive dose of picrotoxin (3 mg/kg, i. p.) significantly increased [35S]TBPS and [3H]muscimol binding in cerebellum (CB) with no change in frontal cortex (FC). In rats treated chronically with picrotoxin (3 mg/kg, i.p., daily for 10 days), theBmaxof [35S]TBPS binding site was significantly decreased in the FC., striatum (ST), and CB with no change inKDvalues. Neither [3H]muscimol binding in the FC and CB nor [3H]fiunitrazepam binding in the FC was affected in these rats. In addition, the potency of pentobarbital to inhibit [35S]TBPS binding in vitro was not altered following acute or chronic treatment of picrotoxin. Chronic administration of picrotoxin did not affect convulsive ED50or LD50of picrotoxin; however, it delayed the onset of convulsions and increased the time to death. These results suggest that treatment with picrotoxin at a subconvulsive dose for 10 days causes down‐regulation of [35S]TBPS binding sites and that this down‐regulation might be related, at least in part, to the decreased extent of convulsant potency of picrotoxin. In addition, the results indicate possible interaction between convulsant binding sites and GABAAreceptor sites in the CB following picrotoxin
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01848.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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10. |
Ribonuclease Activities and Distribution in Alzheimer's and Control Brains |
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Journal of Neurochemistry,
Volume 52,
Issue 4,
1989,
Page 1071-1078
K. Maschhoff,
C. L. White,
L. W. Jennings,
M. R. Morrison‐Bogorad,
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摘要:
AbstractLevels of free and total alkaline ribonuclease, and levels of acidic ribonuclease, were measured postmortem in control brains and in the brains of patients with Alzheimer's disease. In each brain region assayed, whether control or Alzheimer's, there was a statistically significant difference between the levels of free and total alkaline ribonuclease. Between 59 and 90% of the enzyme activity was associated with alkaline ribonuclease inhibitor in an inactive complex. Levels of free and total alkaline ribonuclease varied widely among different brains and brain regions, and were always lower in cerebellum than in temporal cortex and occipital pole. There was no significant difference in the levels of total alkaline ribonuclease, free alkaline ribonuclease, or acidic ribonu‐cleases between corresponding regions of Alzheimer's and control brains. There was also no qualitative difference in the subcellular distribution of the alkaline and acidic ribonucleases between Alzheimer's and control brain. No significant relationships were found between ribonuclease levels and age, neuritic plaque density, postmortem interval, or storage tim
ISSN:0022-3042
DOI:10.1111/j.1471-4159.1989.tb01849.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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