ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13610.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The L1‐ and F11‐like axonal glycoproteins, implicated in neurite outgrowth and fasciculation, are members of the Ig superfamily comprising multiple fibronectin type III‐like domains. Their Ig‐like and fibronectin type III‐related domains are likely to be composed of seven β‐strands arranged in two opposing β‐sheets of highly similar topology. Whereas the F11‐like molecules lack a transmembrane sequence and are anchored in the plasma membrane by a glycosylphosphatidylinositol, the L1 ‐like molecules comprise cytoplasmic domains with highly conserved sequence motifs. Most of the latter proteins occur in different isoforms generated by alternative pre‐mRNA splicing, which has not been documented for molecules of the F11 subgroup. L1 ‐like proteins undergo heterophils as well as homophilic interactions, whereas only the former mode of binding was observed for F11 ‐like proteins. Evidence is accumulating that these Ig superfamily molecules with fibronectin type III‐like domains are interacting in a complex manner with each other and molecules of the extracellular matrix. Investigations assigning structure to function reveal that their individual extracellular domains serve distinct binding activities. Recent studies also suggest that L1 and NCAM are implicated in the transducti

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13611.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:During K+‐induced depolarization of isolated rat brain nerve terminals (synaptosomes), 1 mMBa2+could substitute for 1 mMCa2+in evoking the release of endogenous glutamate. In addition, Ba2+was found to evoke glutamate release in the absence of K+‐induced depolarization. Ba2+(1–10 mM) depolarized synaptosomes, as measured by voltage‐sensitive dye fluorescence and [3H]‐tetraphenylphosphonium cation distribution. Ba2+partially inhibited the increase in synaptosomal K+efflux produced by depolarization, as reflected by the redistribution of radiolabeled86Rb+. The release evoked by Ba2+was inhibited by tetrodotoxin (TTX). Using the divalent cation indicator fura‐2, cytosolic [Ca2+] increased during stimulation by approximately 200 nM, but cytosolic [Ba2+] increased by more than 1 μM. Taken together, our results indicate that Ba2+initially depolarizes synaptosomes most likely by blocking a K+channel, which then activates TTX‐sensitive Na+channels, causing further depolarization, and finally enters synaptosomes through voltage‐sensitive Ca2+channels to evoke neurotransmitter release directly. Though Ba2+‐evoked glutamate release was comparable in level to that obtained with K+‐induced depolarization in the presence of Ca2+, the apparent intrasynaptosomal level of Ba2+required for a given amount of glutamate release was found to be several‐fold higher than

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13612.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:γ‐Preprotachykinin mRNA is the most abundant tachykinin mRNA in rat tissues, but the pathway of posttranslational processing of its translation product is unknown. An antiserum was raised against the synthetic peptide Asp‐Ala‐Gly‐His‐Gly‐Gln‐lle‐Ser‐His [neuropeptide γ‐(1‐9)‐peptide, equivalent to γ‐preprotachykinin‐(72‐80)‐peptide], that showed<1% reactivity with intact neuropeptide γ and other tachykinins. Neuropeptide γ‐(1‐9)‐peptide was detected by radioimmunoassay in relatively high concentrations in extracts of regions of rat brain and gastrointestinal tract. These concentrations correlated with (r = 0.99), but were significantly (p<0.05) less than, the concentrations of neurokinin A‐like immunoreactivity. The neuropeptide γ‐(1‐9)‐like immunoreactivity in an extract of rat brain was eluted from a reverse‐phase HPLC column in a single fraction with the same retention time as synthetic neuropeptide γ‐(1 ‐9)‐peptide. The synthetic peptide did not contract or relax isolated rat trachea, superior mesenteric artery, stomach fundus, or ileum, and the peptide did not affect the ability of neuropeptide 7 to contract the rat fundus. It is concluded that, in rat tissues, Lys70‐Arg71in 7‐preprotachykinin is a major site of posttranslational processing, but the resulting product, neuropeptide γ‐(1‐9)‐peptide, is n

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13613.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Light and serotonin regulate the phase of the circadian rhythm of the isolated eye ofAplysia. To screen for possible protein components of the eye circadian oscillator, we identified a number of proteins whose synthesis was altered in opposite ways by light and serotonin. The cellular function of one of these proteins was investigated by obtaining a partial amino acid sequence of it and by examining its immunoreactivity. A 38‐amino acid sequence was obtained from a 40‐kDa (isoelectric point 5.6) protein. A greater than 60% amino acid identity existed between this sequence and sequences of a family of calcium/phospholipid‐binding proteins called annexins. Furthermore, the 40‐kDa protein reacted with antibodies generated against a conserved amino acid sequence of annexins and with antibodies raised against human annexin I. The identification of the 40‐kDa, light‐ and serotonin‐regulated protein as an annexin led us to hypothesize that arachidonic acid metabolism plays a role in theAplysiaeye circadian system. To test this hypothesis, we examined the ability of an inhibitor of the arachidonic acid metabolic pathway to perturb the eye rhythm. Pulse treatments of isolated eyes with a lipoxygenase inhibitor, nordihydroguaiaretic acid, phase shifted the rhythm. The phase‐shifting ability of nordihydroguaiaretic acid suggests that arachidonic acid and some of its metabolites may play a role in the eye circadian system. The results of our studies raise the possibility that links may exist between the 40‐kDa annexin‐like protein, arachidonic acid metabolism, and the c

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13614.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Injury‐induced efflux of dopamine was compared between two microdialysis preparations. Rats were implanted with guide cannulae 5–10 days prior to microdialysis experiments. In one group, ventral striatal tissue was punctured with stainless steel obturators that remained in place until the day of the experiment. In the other group, the tissue was not punctured until the microdialysis probes were inserted. Rats from each group were dialyzed with calcium‐free artificial extracellular fluid or tetrodotoxin 4 h after probe insertion. In the rats with previously punctured tissue, calcium depletion reduced dialysate dopamine concentrations to 8% of baseline. Dialysis with tetrodotoxin reduced dopamine concentrations to less than 1% of baseline. In the rats with freshly punctured tissue, dopamine concentrations were reduced only to 50% of baseline levels by calcium depletion and to 30% during dialysis with tetrodotoxin. Thus, penetration of the tissue prior to testing can significantly reduce the acute injury‐induced efflux of dopamine. Further, a significant correlation was found between baseline 3,4‐dihydroxy‐phenylacetic acid/dopamine ratios and the efficacy of tetrodotoxin in reducing dialysate dopamine concentrations. Thus, basal 3,4‐dihydroxyphenylacetic acid/dopamine ratios appear to provide an index of the amount of injury‐induced dopamine efflux following

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13615.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The role of dopaminergic innervation on the postnatal developmental expression of D1dopamine receptors was investigated. Bilateral destruction of dopa‐mine‐containing neurons was achieved by treating rats intracisternally with 6‐hydroxydopamine (6‐OHDA) on postnatal day 3, and rats were killed on day 21. To ensure effective reduction of D1receptor activation by residual dopamine, a group of 6‐OHDA‐lesioned rats was given twice daily injections of the D1receptor antagonist SCH‐23390, from day 4 to 20. D1dopamine receptor binding was assessed in the caudate—putamen, nucleus accumbens, and olfactory tubercle by quantitative autoradiographic analysis of [3H]SCH‐23390 binding. In addition, the relative amount of D1Areceptor mRNA was assessed by in situ hybridization of a35S‐labeled riboprobe. In the developing rats, neither the amount of [3H]SCH‐23390 binding nor the amount of D1Areceptor mRNA was altered by 6‐OHDA lesioning followed by chronic treatment with SCH‐23390. Thus, bilateral destruction of dopamine‐containing neurons and treatment with SCH‐23390 in neonatal rats did not interfere with the developmental expression of D1receptors or alter the levels of mRNA that code for this receptor protein. Treatment of intact rats with SCH‐23390 from postnatal day 4 to 20 also did not alter [3H]SCH‐23390 binding or levels of D1receptor mRNA. However, adult rats treated chronically with SCH‐23390 exhibited increased [3H]SCH‐23390 binding but did not show a signifi

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13616.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The binding of [3H]flunitrazepam, [3H]RO 5‐4864, and [3H]PK 11195 to membrane preparations of the retina was studied in the turtle and rabbit. Only a single population of [3H]flunitrazepam binding sites was detected in the turtle, whereas two populations appeared to be present in the rabbit. No specific binding for [3H]RO 5‐4864 and [3H]PK 11195 could be detected in the turtle. In rabbit, both ligands bound with high affinity, revealing a significant population of binding sites (KDvalues of 24 ± 2.3 and 2.2 ± 0.8 nM, and Bmaxvalues of 440 ± 35 and 1,482 ± 110 fmol/mg of protein, respectively). The binding was temperature ‐ and protein‐dependent. Displacement studies showed a similar rank order of potency of various unlabeled ligands against both [3H]RO 5‐4864 and [3H]PK 11195 (PK 11195>Ro 5‐4864>flunitrazepam>flumazenil). These results suggest that peripheral‐type benzodiazepine receptors are present in the retina of the rabbit, but

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13617.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The present study examines the influence of electroconvulsive seizure (ECS), as well as antidepressant drugs, on levels of serotonin2(5‐HT2) receptor mRNA in rat frontal cortex. Using a sensitive RNase protective assay, preliminary studies demonstrated the predicted regional distribution for the 5‐HT2receptor mRNA: levels of 5‐HT2mRNA were highest in frontal cortex (2.58 amol/μg of total RNA), intermediate in neostriatum, thalamus, and midbrain, and lowest in hippocampus, cerebellum, and choroid plexus. Chronic (10 or 14 days), but not acute (1 or 3 days), ECS treatment significantly increased levels of 5‐HT2receptor mRNA. ECS treatment resulted in a similar time‐dependent up‐regulation of 5‐HT2receptor ligand binding; chronic, but not acute, ECS treatment significantly increased levels of [3H]ketanserin ligand binding, confirming previous reports. Northern blot analysis demonstrated that 5‐HT2receptor mRNA occurs as two bands (∼5 and 6 kb in size), both of which were increased by chronic ECS treatment. The influence of antidepressant drug treatments on 5‐HT2receptor mRNA was also examined. Chronic fluoxetine treatment increased levels of 5‐HT2receptor mRNA, although levels of [3H]ketanserin ligand binding were not altered. In contrast, chronic administration of imipramine, mianserin, and tranylcypromine, treatments that decreased ligand binding, did not decrease levels of 5‐HT2receptor mRNA. In fact, mianserin treatment caused a small, but significant, increase in levels of receptor mRNA. The results suggest that ECS up‐regulation of 5‐HT2receptor mRNA could underlie the increased density of 5‐HT2receptor binding sites in response to this treatment, but that other mechanisms likely operate in the down‐regulation of 5‐HT2receptor ligand binding

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13618.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:To determine which portion of a ganglioside molecule might be necessary for the enhancement of recovery from MPTP‐induced lesions, the ability of specific gangliosides to stimulate proliferation of MPTP‐treated 140–3 cells was investigated. The results indicate that of the gangliosides tested, GM1 was the most effective. Although GD1 a and GT1 b were able to enhance the proliferation of MPTP‐treated cells, twice as much GT1b was needed to induce the same effect seen with GM1. In contrast, asialo‐GM1, GM2, and GM3 were ineffective at promoting proliferation of MPTP‐treated cells. The isolated oligosaccharide of GM1 had little effect. These results indicate that in addition to the sialosyl residue, at least the Gal(β1–3)Gal‐NAc portion of the oligosaccharide chain and the ceramide moiety are essential for the induction of proliferation of the MPTP‐treated cells. Investigation of the time of addition of GM1 on its ability to counteract the MPTP‐induced inhibition of 140–3 cell proliferation indicated that addition of GM1 before or concomitantly with MPTP resulted in a significant reduction in MPTP‐induced inhibiti

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1993.tb13619.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY