摘要:

Abstract—The rat brain concentrations of protein, RNA, DNA, putrescine, and of the polyamines spermidine and spermine, were studied during development. Putrescine formation is apparently controlled by ornithine decarboxylase. Spermidine and spermine concentrations change in inverse directions to their anabolic enzymes. It has been presumed, therefore, that the low concentrations of the polyamine‐synthesizing enzymes in immature brain are compensated for, by high putrescine andS‐adenosylmethionine concentrations.In agreement with previous findings for fish brain, the changes in RNA and spermidine concentrations were most closely correlated. The functions of DNA: spermine are directly correlated only during the periods of brain maturation, after cell proliferation has nearly c

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07621.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Glycogen phosphorylase activity and glycogen levels were investigated in the cerebral cortex of mice of two different strains under the influence of homocysteine. Control levels of glycogen and total phosphorylase activity (i. e. activity in the presence of 1 mM‐AMP) were higher in the inbred strain A, whereas a higher proportion of phosphorylase in its active form (activity without 5′‐AMP) was obtained in the ICR strain (probably due to slower fixation of brain in this strain). Changes occurring after the administration of homocysteine were similar in both strains. With the onset of first clonic seizures a marked increase of phosphorylase a occurred (increase 99 per cent in strain A and 46.5 per cent in ICR, respectively). During the latter phase of tonic seizures active phosphorylase a did not significantly differ from control values. Five minutes after the end of a tonic seizure, i. e. when partial recovery could already be observed, a marked decrease of active phosphorylase a in comparison with control values, was evident (decrease against control values of 45.5 per cent in strain A and 30.5 per cent in ICR, respectively). The total phosphorylase activity was not affected in strain A, whereas a slight increase during clonic seizures was seen in the ICR strain. In accordance with the enhanced activation of phosphorylase at the onset of clonic seizures, a marked decrease in glycogen levels (35‐50 per cent) was observed in both strains of mice. This decrease persisted even during the 5 min recovery period. When seizures were prevented by Na phenobarbital or glycine, the activation of phosphorylase was either completely prevented (by a non‐anaesthetic dose of phenobarbital) or reduced (by glycine). The present results have demonstrated that changes in glycogen metabolism occurring during homocysteine seizures differ distinctly from those previously found during seizures induced by methionine sulphoximine, a substance structurally related to h

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07622.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Cyclic‐AMP stimulates phosphorylation of Hf1 and Hf2b histone fractions and of protamine by tubulin preparations. Lyophilization of the tubulin removes the requirement for cyclic‐AMP; the kinase is fully active in the absence of cyclic nucleotide. The casein kinase activity of tubulin is independent of cyclic‐AMP. Only cyclic‐IMP can replace cyclic‐AMP at the low concentrations at which the cyclic‐AMP is effective. 5′‐AMP inhibits basal levels of Hf 1 histone phosphorylation. Several attempts have been made to separate the kinase activity from tubulin. Both tubulin and kinase activity are precipitated by vinblastine. Mg2+precipitation of tubulin inactivates the kinase; there is no evidence that the precipitation step removes the kinase from tubulin. Tubulin which has been assembled into microtubules, collected by centrifugation and disassembled, retains its kinase activity. Kinase activity and tubulin co‐elute from DEAE‐cellulose. Taken together, these experiments demonstrate that tubulin, prepared by fractionation with ammonium sulfate followed by elution from DEAE Sephadex with 0‐8 M KC1 and concentration by reprecipitation with ammonium sulfate has a closely associated, cyclic‐AMP dependent protein kinase activity, which may be intrinsic to the tu

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07623.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Choline acetyltransferase levels have been measured in specific nuclei of the diencephalon. On the whole, the thalamic nuclei contain higher concentrations of this enzyme than do the hypothalamic and preoptic nuclei. Those nuclei which seem to receive the most dense cholinergic innervation contain the highest levels of choline acetyltransferas

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07624.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—The kinetic properties of soluble and membrane‐bound choline acetyltransferase (ChAc) were determined as a function of homogenization media and solubilization procedure in various regions of rat brain. Treatment of homogenate and/or subcellular fractions with KCl, Triton X‐100, or ether dramatically altered the apparentVmaxand the degree of solubilization of the enzyme, but no fraction exhibitedKmvalues substantially different from 12 μM for acetyl‐CoA and 200 μM for choline. On the other hand, increasing the ionic strength of the assay medium for a given fraction from 0‐02 M to 0‐5 M increased bothVmaxandKmvalues for both substrates. The absolute levels and subcellular distribution of ChAc were determined in 11 brain regions to localize cholinergic cell bodies and nerve endings. Levels of ChAc varied from 139 m‐units/g tissue in caudate‐putamen to 5‐7 m‐units/g tissue in cerebellum. The fraction of ChAc activity associated with synaptosomes varied from near 75 per cent in caudate‐putamen, hippocampus and cortical regions to near 20 per cent in septum, locus coeruleus area and substantia nigra area. The apparent parallel distribution of cholinergic and catecholaminergic nerve endings is discussed in terms of a hypothetical model for the pathophysiology and treatment

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07625.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—A simple method for the separation of 5‐hydroxyindoleacetic acid (5‐HIAA) and 5‐methoxyindoleacetic acid (5‐MeOIAA) on columns of non‐ionic polystyrene (Amberlite XAD‐2) is described. Administration of 5‐methoxy‐N, N‐dimethyl‐tryptamine (5‐MeODMT) 2 mg/kg i. p. to rats results in a sixfold increase in brain 5‐MeOIAA within 15 min. This increase is blocked by the selective inhibitor of MAO‐A, clorgyline, but not by the selective inhibitor of MAO‐B, deprenyl, indicating that 5‐MeODMT is deaminated almost entirely by MAO‐A. The apparent 5‐MeOIAA concentration in the brains of L‐tryptophan loaded rats is not reduced by clorgyline and deprenyl, either singly or in combination, indicating that most of this fluorescence is due to other, unidentified substances. The apparent concentration of 5‐HIAA in rat brain, minus 5‐MeOIAA, is unaffected by deprenyl and reduced by clorgyline. However, clorgyline and deprenyl in combination reduced 5‐HIAA values below those obtained with clorgyline alone. It is concluded that very little 5‐MeODMT or other 5‐methoxyindoleamines are formed endogenously in rat brain, and that the stereotyped syndrome of hyperactivity and tremors produced in rats by pretreatment with MAO inhibitors and L‐tryptophan is dependent on the formation of an N‐substituted derivative of 5‐HT w

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07626.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Depressant drugs are considered to exert their pharmacological effects as a result of membrane interactions determined by their physico‐chemical properties. In this study, a correlation was found between lipid solubility and potency of various local anaesthetics, antihistamines, tricyclic antidepressants and phenothiazine tranquilizers as inhibitors of the Na, K‐ATPase activity of a microsomal membrane fraction from bovine brain cortex. Depressant drugs such as chlorpromazine, which have the greatest lipid solubilities, were competitive inhibitors of Na activation but noncompetitive toward K activation, whereas drugs such as tetracaine with lower lipid solubilities were competitive inhibitors of K activation but noncompetitive toward Na activation. Drugs with intermediate lipid solubilities were mixed competitive‐noncompetitive inhibitors of both Na and K activation. Both chlorpromazine and tetracaine competitively inhibited cation activation by a heterotropic allosteric mechanism, probably mediated through membrane conformational changes. Whereas quaternization or a decrease in the incubation pH interfered with the ability of chlorpromazine to inhibit Na activation in a competitive fashion, these changes did not affect the ability of tetracaine to compete with K activation. In addition Mn, Ca and phosphatidyl serine were very effective non‐competitive antagonists of chlorpromazine inhibition of Na, K‐ATPase, whereas these agents competitively antagonized tetracaine inhibition to a lesser extent. These data suggest that the more lipid soluble phenothiazines penetrate into and react in hydrophobic areas of the membrane microenvironment, resulting in a membrane perturbation which interferes with Na activation. On the other hand the less lipid soluble local anaesthetics probably act at superficial sites near the membrane surface, resulting in a different membrane perturbation which interferes with the K activation mechanism. It is suggested that lipid solubility may be a significant factor in determining selectivity in the membrane interactions of various pharmacological agents and hence differences in pharmacological activity among different classes of depre

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07627.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Rat brain SAM levels were markedly increased after methionine administration, whereas the convulsant, L‐methionine‐dl‐sulphoximine (MSO), produced a 35 per cent decrease in whole brain content ofS‐adenosyl‐L‐methionine (SAM). When methionine was given in combination with MSO, SAM levels were not decreased. Studies on the regional distribution of SAM revealed only a small variation between regions (from 24 nmol/g in midbrain to 49‐5 nmol/g in striatum). SAM levels were reduced by about 50 per cent in the cerebellum, striatum, cortex and hippocampus 3 and 6 h after MSO. It is proposed that abberant cerebral methylation processes may be involved in the genesis of

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07628.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Cultures of cloned neuroblastoma cells (N1E) in stationary phase and cloned glioma cells (C21) in confluency showed substantial differences in phospholipid composition. As a percentage of lipid P, N1E contained more phosphatidylcholine, less ethanolamine phosphoglycerides and much less sphingomyelin than C21. When incubated with32Piboth cell lines incorporated comparable amounts of radioactivity into total phospholipids. In NIE, phosphatidylcholine contained much more and phosphatidylinositol and phosphatidic acid somewhat less label as compared to C21. The presence in the incubation medium of either norepinephrine or carbamylcholine failed to elicit stimulation of32P incorporation into any phospholipid clas

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07629.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

Abstract—Neuroblastoma cell cultures took up linoleic and linolenic acids at approximately equal rates, and incorporated them into a variety of lipid fractions, principally cellular phospholipids. Linoleic acid was preferentially incorporated into choline phosphoglycerides, while most of the radioactivity derived from linolenic acid entered ethanolamine phosphoglycerides. There was no evidence for direct transfer of fatty acids between these two phosphoglyceride fractions. When, after the addition of cytosine arabinoside, cell division was arrested, the entry of labelled fatty acids into ethanolamine and serine phosphoglycerides was reduced, suggesting that these lipids are involved in the formation of new cell membranes.In the ethanolamine phosphoglyceride fraction, phosphatidal ethanolamine (plasmalogen) was the principal acceptor for the higher polyunsaturated fatty acids of the φ 3 series. The ratio of labelled fatty acids entering ethanolamine plasmalogens to that entering ethanolamine phosphoglycerides increased following the addition of cytosine arabinoside, suggesting plasmalogens to be involved in formation of cell processes.The first step in the metabolism of both linoleic and linolenic acid was the addition of a two‐carbon unit. Conversion of linoleic acid to higher polyunsaturated fatty acids was slower than the conversion of linolenic acid to its higher analogues. This contrasted with the behaviour of dissociated cultures of normal brain cells which were able to form higher analogues of linoleic and linolenic acids at nearly equal r

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1975.tb07630.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY