Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rotating disk electrode (RDE) voltammetry was used to examine the effect of N-methyl-D-aspartate (NMDA) on the initial velocity of dopamine (DA) uptake in suspensions of rat striatal tissue. Transport velocities were determined by measuring the rate of clearance of 2 microM DA added to the tissue suspension. NMDA (200 microM) was found to increase the initial velocity of DA transport from 548 +/- 28 to 803 +/- 63 pmol/s per g tissue (mean +/- SEM; P < 0.005). The increase was reversed by the competitive NMDA antagonist AP5, and thus appears to be receptor-mediated. In a separate experiment, lower concentrations of NMDA (20-100 microM) yielded a high correlation (r = 0.96; P < 0.05) of velocity versus concentration. Kainic acid (10 microM) also was found to increase the initial rate of uptake, from 505 +/- 34 to 702 +/- 71 pmol/s per g (P < 0.05). The results of this study indicate that the rate of DA uptake in the striatum can be modulated in vitro by presynaptic ionotropic glutamate receptors.
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PMID:Regulation of dopamine uptake in rat striatal tissue by NMDA receptors as measured using rotating disk electrode voltammetry. 891 3

The anticholinergic drug orphenadrine is used in the treatment of Parkinson's disease. In this study we evaluate the neuroprotective effects of orphenadrine on excitotoxicity in vivo and in vitro. Orphenadrine prevented the mitochondrial and the cytoplasmic membrane potential decrease evoked by NMDA (100 microM) in rat dissociated cerebellar granule cells showing an IC50 value of 11.6 +/- 4.7 microM (mean +/- SEM, n = 5) and 13.5 +/- 2.3 microM (n = 3), respectively. Orphenadrine was able to protect cerebellar granule cell cultures from glutamate-induced neurotoxicity. Kainic acid (KA, 10 mg/kg)-induced excitotoxicity was evaluated in vivo using the microglial marker peripheral-type benzodiazepine receptor (PBR) and heat shock protein 72 (HSP72) expression in the hippocampus. The Bmax of PBR for control tissues was 589.1 +/- 40.0 fmol/mg protein (n = 4), increasing to 1692.5 +/- 51.6 fmol/mg protein (n = 5) after the KA treatment. Pretreatment with orphenadrine (10 mg/kg) blocked the KA-induced increase in PBR density. As expected, KA-administration induced the expression of HSP72 that was blocked in the orphenadrine + KA-treated rats. We demonstrate that orphenadrine, interacting at the NMDA receptor, is able to prevent the neurotoxicity mediated by activation at glutamate ionotropic receptors.
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PMID:In vitro and in vivo protective effect of orphenadrine on glutamate neurotoxicity. 1034 Mar 4