Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norepinephrine GABA, cystein and SH-glutathione evoke a considerable decrease in the activity of alkaline RNase in the postmitochondrial fraction of the rat brain homogenate where the complex of this enzyme with its natural cytoplasmic protein inhibitor is preliminarily disturbed by the addition of pCMB. However these substances have no effect on the activity of alkaline RNase and its cytoplasmic protein inhibitor each taken separately. Evidently, the studied preparations may favour the reduction of the native state of the inactive complex of the enzyme with its inhibitor which was preliminarily disturbed by the pCMB addition.
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PMID:[Effect of norepinephrine, GABA and cysteine on the complex of alkaline ribonuclease with its protein inhibitor]. 4 77

During the first 10 days after peripheral deafferentation of the mouse olfactory bulb stereoselective binding of L-[3H]carnosine declines markedly. The initial phase of this decline is due to a decrease in binding site stereoselectivity, which is then followed by a loss of assayable binding sites. The specificity of inhibition of L-[3H]carnosine binding by various peptides is also altered after denervation. Competitive inhibitors of carnosine binding become less potent after denervation, while analogues which are not competitive inhibitors remain equipotent before and after denervation. Several carnosine analogues that are normally poor inhibitors become more potent after denervation. Treatment of bulb membranes with trypsin, RNase and hyaluronidase, but not DNase or collagenase, resulted in significant alterations in carnosine binding. L-, but not D-carnosine, protected the binding site from trypsin digestion, and induced additional binding in bulb membranes in a dose-and temperature-dependent fashion. Preincubation of membranes with L-carnosine also led to the induction of additional carnosine binding in membranes from cerebral cortex, cerebellum and deafferentated bulbs but not from muscle. Bulbs from newborn mice contain about one-half of the adult levels of binding and no significant sex differences in carnosine binding were detected in bulbs from adult rats. L-[3H]carnosine binding was two-fold higher in the anterior compared to the posterior portion of the bulb, but there were no significant differences in binding of opiate, GABA, alpha-adrenergic, muscarinic cholinergic, benzodiazepine of glutamic acid receptor ligands.
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PMID:L-[3H]Carnosine binding in the olfactory bulb. II. Biochemical and biological studies. 48 25

The effect of acetylcholine, norepinephrine, serotonin, GABA and histone preparations on nervous tissue acid ribonuclease activity has been studied. Acetylcholine and serotonin in vitro were found to reduce the leakage of this enzyme out of lysosomes, whereas norepinephrine and histones enhanced it. These agents did not change free acid ribonuclease activity. It is assumed that these neurotransmitters and histones can take part in the regulation of intracellular RNA metabolism in brain tissue by changing the amount of the free acid ribonuclease fraction through affecting lysosome membranes rather than the activity of the free enzyme. GABA changes neither enzyme leakage out of lysosomes nor its activity.
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PMID:[Intracellular influence of different mediators on acid ribonuclease activity in brain tissue]. 415 29

In this study we have shown, by in situ hybridization and RNase protection assay, a significant trkC mRNA increase confined to the dentate gyrus of hippocampus, both after seizures induced by intracerebroventricular injection of kainic acid and bicuculline. Moreover, after bicuculline treatment we observed an earlier increase of trkC mRNA level, which peaked after 3 h and returned back to normal levels by 12 h. In contrast, the kainic acid treatment produced a delayed increase of trkC mRNA, which initiated after 6 h, peaked at 12 h, and returned to normal levels at 24 h. This increase, which involves also trkC mRNA receptor with tyrosine kinase activity, was mediated by non-NMDA receptors and counteracted by GABA potentiating agent diazepam. Using embryonic neuronal cultures from cerebral hemispheres, including hippocampus, we found that glutamate receptor agonists, including glutamate, kainate, NMDA, and t-ACPD, increase trkC mRNA levels with the following rank order of efficacy: NMDA > t-ACPD > kainic acid > glutamate. In conclusion, our data show that trkC mRNA expression in granule cells of the hippocampus dentate gyrus is increased during seizure activity and that it is mediated by non-NMDA receptors.
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PMID:Seizures increase trkC mRNA expression in the dentate gyrus of rat hippocampus. Role of glutamate receptor activation. 856 16

We have recently shown that chronic neurosteroid, 5 alpha 3 alpha, treatment produced down-regulation of the GABA receptor binding and function, and heterologous uncoupling on the GABAA receptor complex in cultured mammalian cortical neurons. In order to explore the underlying mechanism of these observed down-regulation and heterologous uncoupling phenomenon, we investigated the effect of chronic 5 alpha 3 alpha (1 microM; 5 days) treatment on the GABAA receptor subunits mRNA levels, using RNase protection assay. We found that chronic neurosteroid, 5 alpha 3 alpha, treatment decreased the beta- and alpha-subunits mRNA levels while not altering the gamma 2S-subunit mRNA levels in the cortical neurons. The decrease in the beta-subunits mRNA levels suggests a decrease in the presence of the beta-subunits in the composition of GABAA receptors. This phenomenon may explain the down-regulation of the GABAA receptor binding and function. A decrease in the alpha 3-subunit mRNA level suggests a corresponding decrease in the alpha 3-subunit in the composition of GABAA receptor isoforms, relative to other isoforms. This observation may be responsible for the chronic neurosteroid-induced uncoupling and decreased efficacy. In summary, chronic 5 alpha 3 alpha treatment produced down-regulation of the GABAA receptor beta- and alpha-subunit mRNA levels, and these changes may be associated with the down-regulation, heterologous uncoupling, and decreased efficacy of GABAA receptor complex in the cultured mammalian cortical neurons.
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PMID:Down-regulation of the GABA receptor subunits mRNA levels in mammalian cultured cortical neurons following chronic neurosteroid treatment. 888 48

There is considerable evidence that GABAergic neurons play an important role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, and that these neurons may mediate the feedback actions of gonadal steroids on GnRH neurons. The aim of the present study was to investigate whether endogenous changes in ovarian steroid secretion during the estrous cycle influenced GABAergic neuronal activity in the preoptic region of the hypothalamus, and in other steroid-sensitive brain regions. Intact, adult female rats were sacrificed at various times during the days of metestrus or proestrus. GABAergic neuronal activity was estimated by measuring the rate of accumulation of GABA in microdissected brain regions after pharmacological inhibition of GABA degradation. Concentrations of mRNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67) were quantified in microdissected brain regions by a microlysate ribonuclease protection assay. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), GABAergic neuronal activity was significantly reduced during the afternoon of proestrus compared with the morning of either proestrus or metestrus. In the lateral septal nucleus, GABAergic neuronal activity was significantly increased in the afternoon of proestrus compared with the morning. There were no significant effects of time of day or day of estrous cycle in the medial preoptic nucleus, median eminence, ventromedial nucleus, suprachiasmatic nucleus, medial septal nucleus, hippocampus (CA1 region), or cingulate cortex. In the DBB(ovlt), mRNA levels for both GAD65 and GAD67 were significantly reduced in the afternoon of proestrus compared with the afternoon of metestrus. By contrast, there was no change in GAD65 and GAD67 mRNA levels in the cingulate cortex at any of the times examined. These results demonstrate that GABAergic neuronal activity, and mRNA levels for both GAD65 and GAD67, are reduced in the DBB(ovlt) during the afternoon of proestrus. These results support the hypothesis that decreased GABAergic neuronal activity in this region plays a major permissive role in the generation and maintenance of the estrogen-induced LH surge.
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PMID:GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD65 and GAD67) are reduced in the diagonal band of Broca during the afternoon of proestrus. 889 Dec 47

Neuronal precursors and immature cortical neurons actively accumulate Cl- and as a consequence depolarize in response to GABAA receptor activation. With maturity, intracellular Cl- decreases resulting in a shift towards GABAA inhibition. These observations suggest that changes in expression of cation-Cl- cotransporters may have a significant role in the ontogeny of neuronal Cl- homeostasis. Using ribonuclease protection analysis and in situ hybridization we examined the developmental expression of all presently known members of the cation-Cl- cotransporter gene family in rat brain. Of the inwardly directed cotransporters, NKCC-1, NKCC-2, and NCC-1, only NKCC-1 was detected at significant levels in brain. NKCC-1 was expressed in neurons, appearing first in cortical plate but not in ventricular or subventricular zone. Expression levels peaked by the third postnatal week and were maintained into adulthood. The outwardly directed cotransporters, KCC-1 and KCC-2, demonstrated significantly different levels and time courses of expression. KCC-1 was expressed prenatally at very low levels which increased little over the course of development. In contrast, KCC-2 expression appeared perinatally and increased dramatically after the first week of postnatal life. Differential changes in expression of this gene family occurred during periods of critical shifts in chloride homeostasis and GABA response suggestive of a role in these processes. Furthermore the absence of expression of known inwardly directed cotransporters in Cl- accumulating neuroepithelia and lack of evidence for glial expression suggests that as yet unidentified members of this gene family may be involved in chloride homeostasis in immature neuronal precursors and neuroglia.
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PMID:Ontogeny of cation-Cl- cotransporter expression in rat neocortex. 972 31

Chronic ethanol treatment is known to alter gene expression and function of gamma-aminobutyric acid type-A (GABA(A)) receptors. Here we focus on the beta(2) subunit which is widely expressed in the mammalian brain, and plays a key role in the GABA binding site. Previous studies using rodent models of ethanol dependence show either increased or no change of beta(2) subunit mRNA and peptide content following chronic ethanol administration. In humans, polymorphism at the beta(2) subunit is associated with ethanol dependence in some, but not all, populations. In the present study we measured mRNA content in the cerebellum and cerebral cortex using ethanol-naive and ethanol-dependent DBA/2J and C57BL/6J mice. The DBA/2J strain displays severe ethanol withdrawal severity, while the C57BL/6J strain shows milder withdrawal reactions. RNase protection analysis demonstrated that the DBA/2J strain is more sensitive to ethanol-induced increases in beta(2) subunit mRNA content in the cerebellum, showing significant increases at lower blood ethanol concentrations than C57BL/6J mice. The ethanol-induced regulation in C57BL/6J mice appears to be more complex, with decreases in beta(2) subunit mRNA content at low blood ethanol concentrations, and increases at higher concentrations. These data suggest that differences between C57BL/6J and DBA/2J mice in the degree of physical dependence (withdrawal) on ethanol may be related to differential sensitivity to ethanol regulation of beta(2) subunit expression.
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PMID:GABA(A) receptor beta(2) subunit mRNA content is differentially regulated in ethanol-dependent DBA/2J and C57BL/6J mice. 1087 96

GABAergic neurons are estimated to make up more than half of the neuronal population of the hypothalamus and they likely account for some of the structural and functional sexual dimorphisms observed in the mammalian brain. We previously reported sex differences in the rate of GABA turnover in discrete hypothalamic structures of adult rats. In the present study, we extended our search for sex differences in GABA turnover to additional structures, and further determined whether these differences were associated with differences in GAD(65) and or GAD(67) mRNA levels. Utilizing the GABA transaminase inhibition method, we determined GABA turnover in 14 microdissected brain regions. The rate of GABA turnover was about 2-fold greater in male than in diestrous day one (D(1)) female rats in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis [DBB(ovlt)], anteroventral periventricular nucleus (AVPv), median eminence (ME), and dorsomedial portion of the ventromedial nucleus (VMNdm). A sex difference also was noted in the DBB(ovlt) for GAD(65) mRNA determined by microlysate RNase protection assay. Here, GAD(65) levels were almost 2-fold greater in male rats, which suggests that differences in the activity of this GAD enzyme isoform contributes to the difference in turnover in this area. Additionally, in the dorsomedial nucleus (DMN), the GAD(65) mRNA level was significantly higher in female rats, and in the medial amygdaloid nucleus (Am), GAD(67) mRNA was higher in male rats. These data reveal striking sexual dimorphisms in the rate of GABA turnover and in GAD mRNA levels in specific populations of hypothalamic GABAergic neurons. The functional relationships between these GABAergic neurons and sexually dimorphic phenotypes associated with these structures, such as gonadotropin secretion, reproductive behaviors, seizure threshold and others, warrant further investigation.
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PMID:Sex differences in GABA turnover and glutamic acid decarboxylase (GAD(65) and GAD(67)) mRNA in the rat hypothalamus. 1099 32

Spontaneous Ca2+ transients expressed prior to synaptogenesis regulate the developmental appearance of GABA in cultured Xenopus spinal neurons. We find that glutamic acid decarboxylase (GAD) immunoreactivity is also Ca(2+)-dependent and parallels the appearance of GABA. We show that xGAD 67 transcripts first appear in the embryonic spinal cord during the period in which these Ca2+ spikes are generated, in a pattern that is temporally and spatially appropriate to account for differentiation of GABAergic interneurons. RNase protection and competitive quantitative RT-PCR demonstrate that transcript levels are approximately threefold greater when neurons are cultured in the presence of extracellular Ca2+ that permits generation of transients than when cultured in its absence. The frequency of spontaneous Ca2+ spikes plays a crucial role in the regulation of transcripts, since reimposition of Ca2+ transients at the frequency generated in cultured neurons rescues normal expression. We conclude that naturally occurring low frequencies of these Ca2+ transients regulate levels of xGAD 67 mRNA in differentiating neurons.
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PMID:Specific frequencies of spontaneous Ca2+ transients upregulate GAD 67 transcripts in embryonic spinal neurons. 1108 75


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