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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of lead (in vivo) on the uptake of GABA, dopamine, and histidine as a precursor of histamine in synaptosomes obtained from chronically lead-treated rats was studied. 2. Lead decreased the uptake of GABA, increased the uptake of dopamine, and did not change the uptake of histidine. These effects were independent of calcium concentration. 3. Lead administration to the rat changed the morphology of the synaptosomes, as manifested in the decreased number of synaptic vesicles and disturbed mitochondrial structure. 4. The results suggest the existence of several mechanisms of lead toxicity on uptake, related to individual neurotransmitters, which are not necessarily connected with a Pb2+/Ca2+ interaction.
Cell Mol Neurobiol 1994 Dec
PMID:Lead as an inductor of some morphological and functional changes in synaptosomes from rat brain. 764 Dec 30

4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit transcripts. Spectral analysis of GABA- and 4-PIOL-induced current fluctuations evoked in whole-cell recordings showed that three components with mean durations of approximately 0.7, 5, and 50 msec adequately describe the kinetics of the responses induced by both ligands. The contribution of the longest-lasting component was approximately 60% in the spectra of GABA-evoked responses but < 3% in the spectra of 4-PIOL-evoked responses. This is interpreted as a low incidence of long-lasting bursts in 4-PIOL-evoked responses. No difference was evident between the average inferred unitary conductances for 4-PIOL- and GABA-induced channels. These results at the level of the whole cell were confirmed and extended in outside-out single channel recordings. Taken together, the results indicate that the mechanism responsible for the low efficacy of 4-PIOL is the inability to produce frequent bursts of long duration.
Mol Pharmacol 1995 Aug
PMID:The low efficacy gamma-aminobutyric acid type A agonist 5-(4-piperidyl)isoxazol-3-ol opens brief Cl- channels in embryonic rat olfactory bulb neurons. 765 60

The recently discovered endogenous agonist for the cannabinoid receptor, anandamide (arachidonylethanolamide), can be formed enzymatically by the condensation of arachidonic acid with ethanolamine. 5Z,8Z,11Z-Eicosatrienoic acid (mead acid) has been found to substitute for arachidonic acid in the sn-2 position of phospholipids and accumulate during periods of dietary fatty acid deprivation in rats. In the present study, the chemically synthesized ethanolamide of mead acid was evaluated as a potential agonist at the two known subtypes of cannabinoid receptor: CB1 (central) and CB2 (peripheral). This compound was equipotent to anandamide in competing with [3H]CP55,940 binding to plasma membranes prepared from L cells expressing the human CB1 receptor and from ATt-20 cells expressing the human CB2 receptor. Mead ethanolamide was also equipotent to anandamide in inhibiting forskolin-stimulated cAMP accumulation in cells expressing the CB1 receptor. It inhibited N-type calcium currents with a lower potency than anandamide. Mead and arachidonic acid were equally efficacious as substrates for the enzymatic synthesis of their respective ethanolamides in rat and adult human hippocampal P2 membranes. Palmitic acid was not an effective substrate for the enzymatic synthesis of palmitoyl ethanolamide. Mead ethanolamide exhibits several characteristics of a novel agonist to CB1 and CB2 receptors and may represent another candidate endogenous ligand for the CB1 receptor. Due to the anticonvulsant properties of GABA and the positional similarity of L-serine to ethanolamine in membrane phospholipids, these compounds were synthetically coupled to arachidonic acid, and their resulting arachidonamides were tested as potential cannabinoid agonists. The arachidonamides of GABA and L-serine were inactive in both binding and functional assays at the CB1 receptor.
Mol Pharmacol 1995 Aug
PMID:Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors. 765 62

Effect of novel aromatic GABA derivative (AFA) on lipid peroxidation (LP) was studied in the male rats of the Wistar strain. The morphine-received animals had the higher level of LP in blood plasma, decreased level of total antioxidant activity, the increased rate of LP in the ascorbate-induced system in liver homogenate. In the case of AFA administration with morphine, all the above mentioned effects were almost withdrawn.
Biochem Mol Biol Int 1995 May
PMID:Effect of novel aromatic derivative of GABA on lipid peroxidation in chronically morphinized rats. 766 7

A gene library of Streptomyces lividans has been screened for tRNA-encoding genes with labeled Streptomyces tRNA as a probe. By sequence analysis of hybridizing fragments, two single genes have been identified which code for tRNA(Asp) and tRNA(Gly). Associated with the tRNA(Gly) gene, there are three open reading frames (ORFs) which might code for gene products possibly involved in active transport processes through the bacterial membrane. The transcriptional organization of tRNAGly and the following ORFs was examined by high-resolution S1 mapping. A third clone carried a cluster of genes which encode two tRNA(Gln) and three tRNA(Glu). This cluster corresponds to a similar cluster previously described for Streptomyces rimosus [Plohl and Gamulin, Mol. Gen. Genet. 222 (1990) 129-134].
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PMID:Sequences of tRNA-encoding genes and associated open reading frames of Streptomyces lividans. 769 88

Identification of the neurotransmitter receptor subtypes within the suprachiasmatic nuclei (SCN) will further understanding of the mechanism of the biological clock and may provide targets to manipulate circadian rhythms pharmacologically. We have focused on the ionotropic GABA and glutamate receptors because these appear to account for the majority of synaptic communication in the SCN. Of the 15 genes known to code for GABA receptor subunits in mammals we have examined the expression of 12 in the SCN, neglecting only the alpha 6, gamma 3, and rho 2 subunits. Among glutamate receptors, we have focused on the five known genes coding for the NMDA receptor subunits, and two subunits which help comprise the kainate-selective receptors. Expression was characterized by Northern analysis with RNA purified from a large number of mouse SCN and compared to expression in the remaining hypothalamus, cortex and cerebellum. This approach provided a uniform source of RNA to generate many replicate blots, each of which was probed repeatedly. The most abundant GABA receptor subunit mRNAs in the SCN were alpha 2, alpha 5, beta 1, beta 3, gamma 1 and gamma 2. The rho 1 (rho 1) subunit, which produces GABAC pharmacology, was expressed primarily in the retina in three different species and was not detectable in the mouse SCN despite a common embryological origin with the retina. For several GABA subunits we detected additional mRNA species not previously described. High expression of both genes coding for glutamic acid decarboxylase (GAD65 and GAD67) was also found in the SCN. Among the NMDA receptor subunits, NR1 was most highly expressed in the SCN followed in order of abundance by NR2B, NR2A, NR2C and NR2D. In addition, both GluR5 and GluR6 show clear expression in the SCN, with GluR5 being the most SCN specific. This approach provides a simple measure of receptor subtype expression, complements in situ hybridization studies, and may suggest novel isoforms of known subunits.
Brain Res Mol Brain Res 1995 Feb
PMID:GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions. 772 23

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.
Cell Mol Biol (Noisy-le-grand) 1995 Mar
PMID:Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear. 778 31

This study was carried out to investigate whether the increase of GABA levels in spinal cord dorsal horn in response to chronic inflammatory lesions results from an enhanced expression of the gene that governs the production of glutamate decarboxylase (GAD), the enzyme responsible for GABA synthesis. In situ hybridization was used to visualize neurons expressing GAD mRNA within the spinal cord, in both intact rats and in animals bearing chronic monoarthritis induced by intraarticular injection of complete Freund's adjuvant. In control normal animals, neuronal labeling by an antisense oligonucleotide probe occurred throughout the spinal gray matter, except in the motoneuronal pool of Rexed's lamina IX. In treated animals 4 days after the induction of monoarthritis, a significant increase in the number of labeled cells occurred in the superficial laminae (25.3%) and the neck (17.2%) of the ipsilateral dorsal horn at segments L4-L5 which contain the projection domain of the ankle joint. At 2 weeks, values were, respectively, 20.2% and 13.9% over contralateral values, and an increase of 12.4% was found in the ventral horn. At 3 weeks, the ipsilateral increase of labeled cells was restricted to the superficial dorsal horn (15.2%). These findings emphasize the role played by the spinal GABAergic system in the modulation of chronic nociceptive input. It is suggested that the response of the spinal GABAergic system depends on the activation of GAD gene transcription in spinal neurons.
Brain Res Mol Brain Res 1994 Oct
PMID:Expression of GAD mRNA in spinal cord neurons of normal and monoarthritic rats. 785 44

Tolerance to the anticonvulsant effects of carbamazepine (CBZ) in the amygdala kindling paradigm is a contingent process, since it only develops in rats treated with CBZ before the kindling stimulation and not in those animals treated after the stimulation. The present study was designed to investigate the GABAA receptor system in CBZ contingent tolerance. Receptor autoradiography utilizing various radioligands that bind to different components of the GABAA receptor system and in situ hybridization with oligonucleotides that recognize different subunits of the GABAA receptor were performed. Kindling increased binding to benzodiazepine, picrotoxin, and GABA recognition sites selectively in the dentate gyrus of the hippocampus. Kindling also increased levels of mRNA for the alpha 4, beta 1, and beta 3 subunits but did not change alpha 1, alpha 2, or gamma 2 subunit levels. Rats tolerant to CBZ showed decreased [3H]muscimol binding, diazepam-insensitive [3H]Ro 15-4513 binding, and decreased alpha 4 subunit mRNA content compared to non-tolerant rats, whereas [3H]flunitrazepam binding, [35S]TBPS binding, and the levels of beta 1, and beta 3 subunit mRNAs remained elevated. The data suggest an indirect interaction of CBZ with the GABAA receptor system, since CBZ reportedly does not bind to this receptor system.
Brain Res Mol Brain Res 1994 Oct
PMID:Analysis of the hippocampal GABAA receptor system in kindled rats by autoradiographic and in situ hybridization techniques: contingent tolerance to carbamazepine. 785 61

Polyclonal subtype-specific antibodies were developed against three subtypes of GABA transporters (GAT1, GAT2 and GAT3). By immunoblot analysis, each antibody detected a single band that could be blocked by absorption of the antibody with the respective antigen. GAT2 was found in various tissues, while GAT1 and GAT3 were detected only in the brain. GAT1 was distributed throughout the brain with the highest amount in the olfactory bulb, CA3 region of the hippocampus, layer I of the cerebral cortex, piriform cortex, superior colliculus, interpeduncular nucleus and nucleus spinal tract of the trigeminal nerve, while the GAT3 was densely found in the olfactory bulb, thalamus, hypothalamus, pons and medulla, globus pallidus, central gray, substantia nigra, deep cerebellar nuclei and nucleus spinal tract of the trigeminal nerve but not in the hippocampus, cerebral cortex, caudate-putamen and cerebellar cortex. GAT2 immunoreactivity was faint throughout the brain but was concentrated in the arachnoid and ependymal cells. Both GAT1 and GAT3 were found in the neuropil but not in the cell bodies nor in the white matter. These results suggest that GAT1, GAT2 and GAT3 are expressed in different cells and that GAT1 and GAT3 are involved in distinct GABAergic transmission while GAT2 may be related to non-neuronal function.
Brain Res Mol Brain Res 1994 Oct
PMID:Production of specific antibodies against GABA transporter subtypes (GAT1, GAT2, GAT3) and their application to immunocytochemistry. 785 65


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