ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01934.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Cultures of dissociated embryonic rat mesencephalic cells were exposed to 10 μM1‐methyl‐4‐phenylpyridinium (MPP+), a concentration shown earlier to result in loss of>85% of tyrosine hydroxylase (TH)‐positive neurons without affecting the total number of cells observed by phase‐contrast microscopy. To characterize better the selectivity of the toxic action of MPP+, other parameters were measured reflecting survival and function of dopaminergic or nondopaminergic neurons. Exposure of cultures to 10 μMMPP+for 48 h reduced TH activity to 11% of control values without reducing protein levels. [3H]Dopamine uptake was reduced to<4% of control values, whereas the uptake of γ‐[3H]aminobutyric acid ([3H]GABA) was not affected in these cultures. This same treatment failed to reduce the number of cholinergic cells visualized in septal cultures and did not affect either choline acetyltransferase activity or high‐affinity choline uptake. To assess for possible recovery of dopaminergic neurons, cultures were exposed to 10, 1.0, or 0.1 μMMPP+for 48 h and then kept for up to 6 days in MPP+‐free medium. After exposure to 10 μMMPP+, the number of TH‐positive neurons, their neurite density, TH activity, and [3H]dopamine uptake remained at constant, reduced levels throughout the period of observation after termination of exposure, whereas GABA uptake remained normal. Treatment with lower concentrations of MPP+, i.e., 1.0 and 0.1 μM, induced less pronounced dopaminergic toxic effects. However, no recovery was seen after posttreatment incubation in toxin‐free medium. These findings provide evidence that MPP+treatment results in highly selective and irreversible toxicity for cult

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01935.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Several monoclonal antibodies were generated against the major glycoprotein P0of human peripheral nervous system myelin. Antibodies were selected for their reactivity with P0in Western blots. The antibodies were of the immunoglobulin G subclass and reacted with the glycopeptidase F‐treated P0, indicating that the reactive epitope resides in the protein backbone. In fresh frozen and paraffin‐embedded sections of central and peripheral nervous system of rat and human, P0antibody 592 reacted with myelin sheaths of peripheral, but not central, nervous sys

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01936.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:We examined the effects of hypoxia (8% O2) on in vivo tyrosine hydroxylation, a rate‐limiting step for catecholamine synthesis, in the rat adrenal gland. The hydroxylation rate was determined by measuring the rate of accumulation of 3,4‐dihydroxyphenylalanine (DOPA) after decarboxylase inhibition. One hour after hypoxic exposure. DOPA accumulation decreased to 60% of control values, but within 2 h it doubled. At 2 h, the apparentKmvalues for tyrosine and for biopterin cofactor of tyrosine hydroxylase (TH) in the soluble fraction were unchanged, whereas theVmaxvalue increased by 30%. The content of total or reduced biopterin was unchanged, but the content of tyrosine increased by 80%. Tyrosine administration had little effect on DOPA accumulation under room air conditions but enhanced DOPA accumulation under hypoxia. After denervation of the adrenal gland, the hypoxia‐induced increase in DOPA accumulation and in theVmaxvalue was abolished, whereas the hypoxia‐induced increase in tyrosine content was persistent. These results suggest that in vivo tyrosine hydroxylation is enhanced under hypoxia, although availability of oxygen is reduced. The enhancement is the result of both an increase in tyrosine content coupled with increased sensitivity of TH to changes in tyrosine tissue content and of an increase in dependence of TH on tyrosine levels. The increase in the sensitivity of TH and in theVmaxvalue is neurally induced, whereas the increase in tyrosine content is regulated by a different me

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01937.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Myotubes prepared from the Japanese quail embryo at 9 days gestation were cultivated in the presence of glycyl‐L‐glutamine (Gly‐Gln, β‐endorphin C‐terminal dipeptide) or glycyl‐glutamic acid (Gly‐Glu), and changes in the activity of acetylcholinesterase (AChE) molecular forms and binding of125I‐α‐bungarotoxin (αBGT) to cell surface nicotinic acetylcholine receptors were measured. The A12oligomer was the major form of AChE in the cultures. The activity of all molecular forms of the enzyme was increased in the presence of Gly‐Gln, but Gly‐Glu did not alter AChE activity. In cells infected with the temperature‐sensitive mutant, La31C, of Rous sarcoma virus (ts‐RSV) and transferred to the nonpermissive temperature, the A12form of AChE was absent, but its activity could be induced following exposure of the cells to Gly‐Gln. When cells treated in this way were incubated in the presence of collagenase, there was a small but significant loss of A12AChE activity, indicating that Gly‐Gln stimulated the activity of a pool of this oligomer which was mainly but not entirely intracellular. Neither Gly‐Gln nor Gly‐Glu influenced125I‐αBGT binding after exposure of the cells to the peptides for any duration. Neither Gly‐Gln nor Gly‐Glu influenced the accumulation of cyclic AMP in the cultures. β‐Endorphin is one of a family of peptides that coexist transiently with acetylcholine in lower motoneurones of vertebrates in the perinatal period. This report provides evidence for the selective trophic activity of one of its derivatives toward the postsyn

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01938.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:In this study we have used fluoride as a tool to investigate the involvement of G protein‐coupled effector systems in the regulation of the depolarization‐induced release of γ‐aminobutyric acid (GABA) from rat cerebral cortex. To distinguish among the activating effects of NaF on G proteins linked to different effectors, such as adenylate cyclase, polyphosphoinositide phospholipase C, and K+channels, agents specific to these effectors have been used in parallel. NaF induced a marked dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, with an EC50of 1.26 mM, increasing release by 103% at 5 mMNaF. No effect on basal release was seen up to 3 mMNaF, and no modulation of [3H]acetylcholine (ACh) release was seen up to 5 mMNaF. Phorbol 12,13‐diacetate (PDA) produced a similar dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, potentiating the release of [14C]GABA by 50% at 10 μMPDA. The phosphodiesterase inhibitors, 3‐isobutyl‐1‐methylxanthine (IBMX) and theophylline, inhibited the K+‐evoked release of [14C]GABA, and IBMX reversed the NaF facilitation of GABA release in a dose‐dependent manner (pA22.57). The K+channel blocker (IAcurrent) tetrahydroaminoacridine (THA), which markedly inhibits the K+‐evoked release of [14C]GABA, also reversed the NaF facilitatory effect, but the release of [3H]ACh was less sensitive to the inhibitory effect of THA. On the other hand, the K+channel blocker, tetraethylammonium, which has no effect on the release of [14C]GABA, caused a significant facilitation of K+‐evoked release of [3H]ACh. From these studies, it is concluded that GABA release in cerebral cortex is subject to regulation by G protein‐linked effector systems that are distinct from those affecting the rele

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01939.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Previous studies have shown that nutritional iron deficiency in rats reduces brain iron content, resulting in dopamine D2receptor subsensitivity, as indicated by a decrease in [3H]spiperone binding in caudate nucleus and in behavioral responses to apomorphine. Both phenomena can be reversed by iron supplementation. The possibility that neuroleptic‐induced dopamine D2receptor supersensitivity involves an alteration in brain iron content was investigated in nutritionally iron‐deficient and control rats chronically treated with haloperidol (5 mg/kg daily for 14 or 21 days). Neuroleptic treatment was initiated either (a) concurrently with iron deficiency or (b) 2 weeks after the start of iron deficiency. The results show that dopamine D2receptor subsensitivity, a feature of iron deficiency, is absent in haloperidol‐treated, iron‐deficient groups. On the contrary, these animals demonstrated biochemical and behavioral dopamine D2receptor supersensitivity that is relatively greater than that observed with control, haloperidol‐treated animals. Haloperidol (5 mg/kg daily for 21 days) as well as chlorpromazine (10 mg/kg daily for 21 days) caused a significant reduction (20–25%) in liver nonheme iron stores as compared with values in control rats. However, in iron‐deficient rats, in which liver iron stores were almost totally depleted, haloperidol had no effect. The ability of chronic haloperidol treatment to prevent the reduction of dopamine D2receptor number during iron deficiency may be associated with alteration of body iron status. Thus, less iron may result in an increase in free haloperidol available to the dopami

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01940.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Glycine was taken up by a synaptic vesicle fraction from spinal cord in a Mg‐ATP‐dependent manner. The accumulation of glycine was inhibited by carbonyl cyanide‐m‐chlorophenylhydrazone (CCCP) and nigericin, agents known to destroy the proton gradient across the vesicle membrane. Vesicular uptake of glycine was clearly different from synaptosomal uptake, with respect to both the affinity constant and the effect of Na+, ATP, CCCP, and temperature. Oligomycin and strychnine did not inhibit the vesicular uptake, showing that neither mitochondrial H+‐ATPase nor binding to strychnine‐sensitive glycine receptors was involved. It is suggested that the vesicular uptake of glycine is driven by a proton gradient generated by a Mg2+‐ATPase. A low concentration of Cl‐had little effect on the uptake of glycine, whereas the uptake of glutamate in the same experiment was highly stimulated. High concentrations of γ‐amino‐n‐butyric acid and β‐alanine inhibited vesicular glycine uptake, but glutamate did not. Accumulation of glycine was found to be fourfold higher in a spinal cord synaptic vesicle fraction than in a vesicle frac

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01941.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Concentrations of dopamine (DA), its metabolites 3‐methoxytyramine and homovanillic acid (HVA), noradrenaline (NA), its metabolites normetanephrine (NM) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), 5‐hydroxytryptamine (5‐HT, serotonin), and its metabolite 5‐hy‐droxyindoleacetic acid (5‐HIAA) were measured in 14 brain regions and in CSF from the third ventricle of 27 human autopsy cases. In addition, in six cases, lumbar CSF was obtained. Monoamine concentrations were determined by reversed‐phase liquid chromatography with electrochemical detection. Ventricular/lumbar CSF ratios indicated persistence of rostrocaudal gradients for HVA and 5‐HIAA post mortem. Ventricular CSF concentrations of DA and HVA correlated positively with striatal DA and HVA. CSF NA correlated positively with NA in hypothalamus, and CSF MHPG with levels of MHPG in hypothalamus, temporal cortex, and pons, whereas CSF NM concentration showed positive correlations with NM in striatum, pons, cingulate cortex, and olfactory tubercle. CSF 5‐HT concentrations correlated positively with 5‐HT in caudate nucleus, whereas the concentration of CSF 5‐HIAA correlated to 5‐HIAA levels in thalamus, hypothalamus, and the cortical areas. These data suggest a specific topographic origin for monoamine neurotransmitters and their metabolites in human ventricular CSF and support the contention that CSF measurements are useful indices of central

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01942.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:Interactions of the potent phencyclidine receptor agonist MK‐801 with the dopaminergic system were examined in various brain regions in the rat. MK‐801 increased dopamine (DA) metabolism in the pyriform cortex, entorhinal cortex, prefrontal cortex, striatum, olfactory tubercle, amygdala, and septum without affecting DA metabolism in the cingulate cortex and nucleus accumbens. In pyriform cortex and amygdala, MK‐801 was more potent than phencyclidine at increasing DA metabolism. Local injections of MK‐801 into ventral tegmental area and into the amygdala/pyriform cortex interface indicated that MK‐801 may act at the cell body as well as the nerve terminal level to increase DA metabolism and that ongoing dopaminergic neuronal activity is a prerequisite for full dr

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1990.tb01943.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY