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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the N-methyl-D-aspartate receptor gene during long-term administration of competitive and non-competitive NMDA antagonists was studied in rat brain using antisense cRNA transcribed from reverse transcriptase-polymerase chain reaction (RT-PCR)-generated rat NMDA receptor cDNA. Unlike non-competitive antagonists, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) markedly decreased NMDA receptor mRNA steady-state concentrations in frontal cortex and hippocampus. Our results are consistent with a regulation of the NMDA receptor at the level of gene expression.
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PMID:3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid decreases NMDA receptor mRNA. 142 22

Effects of pentamidine, a therapeutic drug for Pneumocystis carinii pneumonia (PCP) in acquired immunodeficiency syndrome (AIDS), on specific bindings of [3H](+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,11-imine maleate (MK-801) and [3H]nitrendipine were investigated in crude synaptic membranes (CSM) of rat brain. Pentamidine inhibited [3H]MK-801 binding but did not change [3H]nitrendipine binding, although neither binding was inhibited by 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxycytidine (inhibitors for reverse transcriptase of HIV-1), or FK-506 or cyclosporin A (immunosuppressants). In Triton X-100-treated CSM (post-synaptic density-rich fractions), the inhibitory effect of pentamidine on [3H]MK-801 binding was partially prevented by addition of spermine and NMDA plus glycine (Gly). Electrophysiological experiments showed that pentamidine also inhibited Ca(2+)-current evoked by NMDA plus Gly in Xenopus oocytes injected with rat brain mRNA. These results suggest that pentamidine is a potent inhibitor for NMDA receptor/channels.
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PMID:Inhibitory effects of pentamidine on N-methyl-D-aspartate (NMDA) receptor/channels in the rat brain. 774 90

Before becoming acyclic, middle-aged rats display an attenuated LH surge and a decreased number of activated GnRH neurons. The present study examined whether the decreased activation of GnRH neurons in middle-aged rats could be due to defective glutamate neurosignaling in the hypothalamus. Arcuate nucleus/median eminence (ARC/ME) fragments were isolated from young (2-month-old) and middle-aged (9- to 11-month-old) rats at 1700 h on proestrus and incubated in vitro with or without the specific glutamate agonists, D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (1 mM), kainate (1 mM), and N-methyl-D-aspartate (NMDA; 50 mM). The results showed that basal GnRH release was similar in the two age groups. In contrast, stimulated GnRH release by D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCl stimulation at the end of the experiments confirmed the viability of all ARC/ME fragments. Quantitative reverse transcriptase-PCR revealed that messenger RNA levels for the major NMDA receptor subunit (NMDAR1) were significantly lower in the preoptic area and ARC/ME of the middle-aged rat on proestrus afternoon. As a whole, these findings suggest that a defect in hypothalamic glutamate neurosignaling may be an important mechanism leading to age-related defects in LH secretion and acyclicity in female animals.
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PMID:Decreased gonadotropin-releasing hormone neurosecretory response to glutamate agonists in middle-aged female rats on proestrus afternoon: a possible role in reproductive aging? 864 Nov 83

1. The Ca2+ permeability of non-NMDA and NMDA receptor channels was studied using a fluorometric flux measurement approach in somata and dendrites of CA1 pyramidal neurones in rat hippocampal slices. For this purpose, the Ca2+ fraction of the total cation current (named 'fractional Ca2+ current') was measured directly from the change in the Ca(2+)-sensitive fura-2 fluorescence at 380 nm excitation wavelength. 2. The fractional Ca2+ current through the somatic NMDA receptor channels was 10.69 +/- 2.13% (mean +/- S.D.) and that through dendritic receptor channels was 10.70 +/- 1.96%. The fractional Ca2+ current was not dependent on the extracellular Mg2+ concentration and its voltage dependence was in agreement with the Goldman-Hodgkin-Katz current equation. 3. AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) or kainate applications produced small but significant Ca2+ entry. Fractional Ca2+ currents of 0.58 +/- 0.34% were measured for somatic AMPA applications, 0.68 +/- 0.20% for somatic kainate applications, 0.66 +/- 0.25% for dendritic AMPA applications and 0.61 +/- 0.16% for dendritic kainate applications. 4. The expression pattern of glutamate receptor subunits encoding messenger ribonucleic acids (mRNAs) was analysed with the single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) approach applied to CA1 pyramidal neurones. The AMPA receptor subunits GluR-A, GluR-B and GluR-C, and the NMDA receptor subunits NR2A and NR2B were found to be abundantly expressed in all CA1 pyramidal neurones tested. 5. This study establishes the fractional Ca2+ current through somatic and dendritic NMDA and non-NMDA receptor channels in CA1 pyramidal neurones. The dendritic, presumably synaptic, NMDA receptor channels are highly Ca2+ permeable and have a fractional Ca2+ current closely resembling that of somatic extrasynaptic NMDA receptor channels. Both somatic and dendritic non-NMDA receptor channels are of the 'low Ca2+ permeable' type and have a fractional Ca2+ current that is about twenty times smaller than that of NMDA receptor channels.
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PMID:Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones. 881 9

Subtypes I, II and III of sodium channel alpha-subunit mRNAs were analyzed in adult rat brain areas after kainate-induced seizures. Tissue samples were microdissected from occipital neocortex, CA1 and CA3 hippocampus areas and dentate gyrus. Three reverse transcriptase-polymerase chain reaction (RT-PCR) protocols were undertaken to amplify these mRNAs. Amplification products were then distinguished after digestion by restriction enzymes, electrophoresis separation and densitometric analysis of gel profiles. PCR 1 evidenced the relative percentage of mRNAs I, II and III as well as neonatal II and III subtype isoforms, which resulted from an alternative splicing. PCR 2 and 3 were performed to focus on the neonatal vs. adult ratio in II and III subtypes, respectively. Seizures were shown to induce an increase in both neonatal subtypes, which suggested an alteration at the splicing level. These changes exhibited a peculiar brain regional distribution, the maximal effect being observed in dentate gyrus and hippocampus CA1 area. In situ hybridization experiments, using a digoxigenin-labeled oligonucleotide probe-specific for neonatal II and III mRNAs, confirmed this increase in neonatal mRNA subtypes. These changes were transient, reaching a maximum 6 h after drug injection, then disappearing between 12 and 48 h. They were prevented by a pre-treatment of animals by MK-801, a non-competitive antagonist of NMDA receptors. This work, thus, suggested that KA-induced seizures can be accompanied by transient alteration in the splicing pattern of sodium channel alpha-subunit mRNAs which resulted in an increase in expression of their neonatal isoforms within localized areas of adult rat brain.
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PMID:Increase in mRNAs encoding neonatal II and III sodium channel alpha-isoforms during kainate-induced seizures in adult rat hippocampus. 907 59

Two adeno-associated virus (AAV)-derived plasmids were constructed with portions of the N-methyl-d-aspartic acid-R1 (NMDA-R1) receptor subunit downstream from the AAV p40-(pJDT95dlk-aR1) or cytomegalovirus (CMV) promoter (pTRUF3-aR1) in an antisense orientation. Each plasmid drove expression of antisense NMDA-R1 in primary rat neocortical neuronal cultures 4 days after transfection as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Transfection with pTRUF3-aR1 (2x4 microgram) but not with pJDT95dlk-aR1 decreased neuronal [3H]MK-801 binding in a dose-dependent manner.
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PMID:Reduced MK801 binding in neocortical neurons after AAV-mediated transfections with NMDA-R1 antisense cDNA. 951 73

Quantitative reverse transcriptase - polymerase chain reaction was used to analyze the relative expressions of NR1, NR2A, NR2B, NR2C, NR2D, and NR3 subunits of the NMDA receptor in the piriform, entorhinal, visual, and motor cortices as well as in the olfactory bulb of adult rat. The analysis detected clear differences in the relative proportions of the NMDA receptor subunits between the five forebrain regions examined. These differences were particularly striking when the piriform and motor cortices were compared. In the piriform cortex, NR1 was the predominant transcript. The expression of NR2A was only slightly higher than half of that of NR1. NR2B was expressed even at lower levels ( approximately 30% of NR1). NR2C and NR3 were expressed at levels which were approximately 15% of those of NR1. NR2D had the lowest levels of expression ( approximately 3% of NR1). In contrast, NR2B was the predominant transcript in the motor cortical region, where it was expressed at the levels close to 135% of those of NR1 message. NR2A had the levels of expression of approximately 50% of those of NR1. The NR2C expression was close to 25% that of NR1, and the NR2D and NR3 transcripts were totally absent from this cortical area. These findings suggest a significant regional variability of the NMDA receptors in the adult rat forebrain.
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PMID:Expression of NR1, NR2A-D, and NR3 subunits of the NMDA receptor in the cerebral cortex and olfactory bulb of adult rat. 1065 28

Whole-cell patch-clamp recordings were performed on 12- to 15-day-old rat locus coeruleus neurones in a midpontine slice preparation. Application of noradrenaline (100 microM) and N-methyl-D-aspartate (NMDA; 100 microM) induced a small outward current and a distinct inward current, respectively. Single-cell reverse transcriptase-polymerase chain reaction (scRT-PCR), used to analyse the expression pattern of NMDA receptor subunits 2A, 2B, and 2C (NR2A-C) subsequent to electrophysiological characterization, demonstrated differences in the capacity of individual locus coeruleus neurones to express NR2A-C mRNA. NR2C mRNA expression predominated over those of NR2A and NR2B mRNA in most neurones. In addition, in neurones containing NR2C mRNA NMDA induced significantly larger currents than in cells lacking expression of this gene. RT-PCR studies performed on tissue preparations of adult rats also revealed a distinct expression of NR2C mRNA. In conclusion, the present data demonstrate differences in the mRNA expression pattern of NR2A-C of individual locus coeruleus neurones with a predominant NR2C mRNA expression in the majority of the cells.
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PMID:Single-cell RT-PCR analysis of N-methyl-D-aspartate receptor subunit expression in rat locus coeruleus neurones. 1119 30

The N-methyl-D-aspartate receptor (NMDA-R) is fully functional in the rat early in embryogenesis, and diverse neuronal plasticity events are regulated through its activation later in postnatal development. On the other hand, systemic administration of glutamate (Glu) to rats at birth induces neuronal degeneration in glutamatergic central nervous system regions via Glu receptor activation. However, it is not known whether an increase in neonatal Glu levels modifies the gene expression of NMDA-R subunits, or if these putative changes are related to gamma-aminobutyric acid-mediated (GABAergic) neurotransmission. We measured, by means of semi-quantitative reverse transcriptase polymerase chain reaction, changes in gene expression of the NMDA-R subunits: NMDA-R1, NMDA-R 2A and NMDA-R 2B in cerebral cortex (CC), striatum (ST) and hippocampus (HP) in the brains of rats treated neonatally with monosodium L-glutamate (MSG). These studies were supported by histological and quantitative analysis of the glia. Our results showed histological evidence of neuronal damage, and increased glial cell number and activity were detected. This was seen mainly in the ST and HP of MSG-treated animals. Significant increases in NMDA-R1, 2A and 2B subunits gene expression was also observed in ST and HP but not in CC, where only NMDA-R 2B was increased in MSG-treated rats. Our data suggest that increases in Glu levels and activation of Glu-receptors after neonatal administration of MSG induce an increase in glial cell reactivity and important changes in NMDA-R molecular composition, with signs of neuronal damage.
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PMID:Changes in NMDA-receptor gene expression are associated with neurotoxicity induced neonatally by glutamate in the rat brain. 1131 43

N-methyl-D-aspartate receptors (NRs) are a group of ionotropic glutamate receptors in the brain and they are composed of heteromeric subunits (NR1, NR2A-D and NR3). In the neostriatum, a brain region that is associated with movement in animals, NMDA channels are known to involve in the motor control. Our previous report (Lai et al., 2000, Neuroscience 98, 493-500) has shown that a single dose of antisense oligodeoxynucleotides that are specific to NR1 subunit results in blockage of the gene expression of NR1 as well as NR2A subunits in the neostriatum. In the present study, antisense oligodeoxynucleotides that are specific to NR2B (ANR2B) were then employed as molecular tools to further investigate the molecular interactions of NMDA receptor subunits in the neostriatum. A single dose of ANR2B was injected unilaterally into the rat neostriatum. After one day of injection, no modification of motor behavior was found in the ANR2B-injected rats. The mRNA level of NR2B in the ANR2B-injected neostriatum was found to be decreased (-20.4%) by reverse transcriptase polymerase chain reaction (RT-PCR). However, the mRNA levels of NR1, NR2A, NR2C and NR2D in the ANR2B-treated neostriatum were found to be unchanged. After two days of injection, NR2B immunoreactivity was found to decrease in the ANR2B-treated neostriatum by immunofluorescence (-35.1%). At higher magnification, NR2B immunoreactivity was found to decrease in presumed spiny neurons of the neostriatum (-23.4%). No change in NR1 immunoreactivity was observed. These results indicate that a single dose of ANR2B can successfully block the gene expression of NR2B in neurons of the neostriatum and there is less effect on NR1 and other NR2 subunits. The blockage of the gene expression of NR2B is therefore specific and the present results may provide important implications in applications of antisense in research and in clinical therapy of neurological diseases.
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PMID:Modulation of the gene expression of N-methyl-D-aspartate receptor NR2B subunit in the rat neostriatum by a single dose of specific antisense oligodeoxynucleotide. 1155 72


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