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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

Trimethylolpropane phosphate (TMPP) is a neuroactive organophosphate generated during partial pyrolysis of a synthetic ester turbine engine lubricant. While TMPP had been shown to have little affinity for acetylcholinesterase, previous binding studies and 6Cl- flux measurements have implicated TMPP as an antagonist of GABA, receptor/Cl- channels. Using the whole-cell patch clamp method, spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by bicuculline-sensitive GABA(A) receptors were measured in neurons cultured from the rat embryonic hippocampus for 13-21 days. Experiments were conducted in the presence of tetrodotoxin and 6-cyano-7-nitroquinoxaline to inhibit spontaneous presynaptic action potentials and glutamate transmission, respectively, thus isolating GABAergic sIPSCs for study. TMPP induced a concentration-dependent inhibition of sIPSC amplitude and frequency suggesting both postsynaptic and presynaptic actions. Administration of 5 microM TMPP reversibly diminished sIPSC amplitude by 23 +/- 8% (mean SEM, n=5 cells) while markedly decreasing the mean sIPSC frequency by 40 +/- 2% (n=5). The mean time constant of sIPSC decay was reversibly decreased by 20 +/- 4% (n=3) in the presence of 20 microM TMPP, suggesting an increase in the rate of inactivation. To directly verify the blockade of ionotropic GABA receptors by TMPP, the effects of TMPP were examined on whole-cell Cl- current responses activated by exogenous GABA. Administration of TMPP (5 microM) depressed peak whole-cell GABA-induced currents to 73 1% (n=4) of control levels, consistent with the results on sIPSC amplitude. Our data directly demonstrate that TMPP directly inhibits GABA(A) receptor function, as indicated by the blockade of whole-cell GABA-mediated Cl- current and the reduction in sIPSC amplitude. Furthermore, TMPP exerts a presynaptic effect on GABAergic transmission, as evidenced by the reduction in sIPSC frequency, which may be independent of a GABA(A) receptor. The molecular basis for the presynaptic action of TMPP remains to be elucidated.
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PMID:Inhibition of spontaneous GABAergic transmission by trimethylolpropane phosphate. 1059 20

To examine the involvement of different ionotropic glutamate receptors in the mediation of responses evoked by noxious cutaneous stimulation, single unit recordings were made from 31 neurons in the primary somatosensory (SI) cortex of rats anesthetized with urethane. To compare synaptic receptor pharmacology across somatosensory submodalities, 13 of the neurons were also tested with an innocuous, cutaneous air jet stimulus. Mechanical (HT) responses, evoked by a 5-s noxious pinch, decayed gradually upon termination of the stimulus and lasted on average for 15.1+/-1.9 s (+/-SEM; n=10). An increase in baseline activity was also observed during noxious stimulus trials of 5-min stimulus intervals. A correlation between increase in mechanical or thermal HT responses and baseline activity was found for some neurons. However, the normalized ratios of the mechanical or thermal HT response to baseline activity during iontophoretic application of (RS)-3-(2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP), an N-methyl-D-aspartic acid (NMDA) receptor antagonist (0.6+/-0.1; n=11, or 6-nitro-7-sulfamoylbenz[f]quinoxaline-2,3-dione (NBQX), an (RS)-alpha-amino-3-hydroxy5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist (0.8+/-0.1; n=11), suggest that the reductions in baseline activity did not account for the reductions of the mechanical or thermal HT responses observed, which were reduced proportionally more than the baseline activity. A 10-ms air jet evoked a biphasic increase in action potentials above an average background activity of 7+/-2 spikes/s (n=13). The early phase of this low-threshold (LT) response was within two or three 10-ms bins and had an average firing rate of 74+/-11 spikes/s evoked in the first 10-ms bin (n=13). In eight neurons, the early LT response was followed by a lower frequency excitatory component lasting an average of 415+/-92 ms. Iontophoretic application of CPP reduced responses evoked by a noxious pinch (21+/-10% of control responses; n=19) and a noxious thermal stimulus (24+/-18%; n=5). The fast component of the LT responses was only reduced to 85+/-4% (n=12). A slower component of the LT responses, when present, was also reduced by CPP (15+/-19%; n=4). Iontophoretic application of NBQX reduced responses evoked by a noxious pinch (42+/-12%; n=19) and a noxious thermal stimulus (63+/-16%; n=8). The fast component of the LT responses was reduced to 43+/-6% (n=12) and the slower component to 32+/-20% (n=6). These data show that both NMDA and AMPA/kainate receptors are involved in the mediation of SI high-threshold responses. This same combination of glutamate receptors also mediates low-threshold synaptic responses.
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PMID:Ionotropic glutamate receptor-mediated responses in the rat primary somatosensory cortex evoked by noxious and innocuous cutaneous stimulation in vivo. 1078 44

Inhibition of kynurenine 3-hydroxylase suppresses quinolinic acid synthesis and, therefore, shunts all kynurenine metabolism toward kynurenic acid (KYNA) formation. This may be a pertinent antiexcitotoxic strategy because quinolinic acid is an agonist of NMDA receptors, whereas kynurenic acid antagonises all ionotropic glutamate receptors with preferential affinity for the NMDA receptor glycine site. We have examined whether the kynurenine 3-hydroxylase inhibitor Ro 61-8048 increases extracellular (KYNA) sufficiently to control excessive NMDA receptor function. Microdialysis probes incorporating an electrode were implanted into the striatum of anaesthetised rats, repeated NMDA stimuli were applied through the probe, and the resulting depolarisation was recorded. Changes in extracellular KYNA were assessed by HPLC analysis of consecutive dialysate samples. Ro 61-8048 (42 or 100 mg/kg) markedly increased the dialysate levels of KYNA. The maximum increase (from 3.0 +/- 1.0 to 31.0 +/- 6.0 nM; means +/- SEM, n = 6) was observed 4 h after administration of 100 mg/kg Ro 61-8048, but the magnitude of the NMDA-induced depolarisations was not reduced. A separate study suggested that extracellular KYNA would need to be increased further by two orders of magnitude to become effective in this preparation. These results challenge the notion that kynurenine 3-hydroxylase inhibition may be neuroprotective, primarily through accumulation of KYNA and subsequent attenuation of NMDA receptor function.
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PMID:Kynurenine 3-hydroxylase inhibition in rats: effects on extracellular kynurenic acid concentration and N-methyl-D-aspartate-induced depolarisation in the striatum. 1108 Jan 94

The circadian pacemaker housed in the suprachiasmatic nucleus (SCN) synchronizes daily sleep-wake cycles, presumably by modulating the sleep-wake regulatory system, including ventrolateral preoptic area (VLPO) neurons. We used whole-cell patch-clamp recording to study the projections from the SCN to the VLPO in horizontal slices of rat hypothalamus. Single-pulse stimulation of the SCN region elicited postsynaptic currents (PSCs) in 20 of 66 neurons (30%) recorded within the VLPO region as verified by intracellular biocytin labelling. At a holding potential of -60 mV, the evoked PSCs had an amplitude of 17.6 +/- 3.2 pA (SEM) and a latency of 6.3 +/- 0.5 ms (n = 10). There was a trend for simple excitatory postsynaptic currents (EPSCs) to be evoked in the VLPO cluster, simple inhibitory postsynaptic currents (IPSCs) in the extended VLPO, and a combination of EPSCs and IPSCs in both regions. IPSCs were blocked reversibly by bicuculline (10 microm, n = 11). In both the presence and absence of bicuculline, EPSCs had fast and slow components that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microm; n = 7), and (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 microm, n = 6), respectively. Reversal potentials for the evoked IPSCs and EPSCs were consistent with mediation via GABAA and ionotropic glutamate receptors, respectively. These results suggest that the SCN region provides both inhibitory and excitatory inputs to single VLPO neurons, which are mediated, respectively, by GABAA receptors and by both non-NMDA and NMDA glutamate receptors. These projections may play important roles in conveying circadian input to systems in the preoptic area that regulate sleep and waking.
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PMID:Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat. 1170 55

The nucleus tractus solitarius (NTS) plays an important role in the control of autonomic reflex functions. Glutamate, acting on N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic receptors, is the major neurotransmitter in this nucleus, and the relative contribution of each receptor to signal transmission is unclear. We have examined NMDA excitatory postsynaptic currents (NMDA-EPSCs) in the subpostremal NTS using the whole cell patch clamp technique on a transverse brainstem slice preparation. The NMDA-EPSCs were evoked by stimulation of the solitary tract over a range of membrane potentials. The NMDA-EPSCs, isolated pharmacologically, presented the characteristic outward rectification and were completely blocked by 50 microM DL-2-amino-5-phosphonopentanoic acid. The I-V relationship of the NMDA response shows that current, with a mean (+/- SEM) amplitude of -41.2 +/- 5.5 pA, is present even at a holding potential of -60 mV, suggesting that the NMDA receptors are weakly blocked by extracellular Mg2+ at near resting membrane potentials. This weak block can also be inferred from the value of 0.67 +/- 0.17 for parameter delta obtained from a fit of the Woodhull equation to the I-V relationship. The maximal inward current measured on the I-V relationship was at -38.7 +/- 4.2 mV. The decay phase of the NMDA currents was fitted with one exponential function with a decay time constant of 239 +/- 51 and 418 +/- 80 ms at a holding potential of -60 and +50 mV, respectively, which became slower with depolarization (e-fold per 145 mV). The biophysical properties of the NMDA receptors observed in the present study suggest that these receptors in the NTS contain NR2C subunits and may contribute to the synaptic signal integration.
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PMID:Electrophysiological evidence for the presence of NR2C subunits of N-methyl-D-aspartate receptors in rat neurons of the nucleus tractus solitarius. 1566 96

The aim of the present study was to provide a "proof of concept" of colon delivery of beta-lactamases by pectin beads aiming to degrade residual beta-lactam antibiotics, in order to prevent the emergence of resistant bacterial strains. Pectin beads were prepared according to ionotropic gelation method using CaCl2 as a gelling agent. Particles were then washed and soaked in polyethylenimine (PEI). Coating beads with PEI considerably improved their stability in simulated intestinal medium. In vitro studies showed that beta-lactamases were released from pectin beads in colonic medium due to the action of pectinolytic enzymes. When ampicillin was added to this medium, the release of beta-lactamases induced, as expected, the antibiotic inactivation. Finally, after oral administration of loaded-beads to CD1 mice, beta-lactamases were retrieved in high concentrations in faeces. Observation by SEM of beads extracted from mice intestinal tracts concluded the core degradation of beads without any modification of the PEI coating layer. This study demonstrates that a multiparticulate system with suitable characteristics for site-specific colonic delivery can be prepared. This system could be used to target beta-lactamases to the colon in order to hydrolyse antibiotic residues during treatment and prevent their impact on colonic microflora.
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PMID:In vitro and in vivo evaluation of pectin beads for the colon delivery of beta-lactamases. 1619 71

Sperm nicotinic acetylcholine receptors (nAChRs) can influence motility and the initiation of acrosome reaction (AR). We report that AR initiation by acetylcholine (ACh) in capacitated human sperm requires both Na+ and Ca2+ in the external medium. Pre-incubation with 50 microM 3-quinuclidinyl benzilate (QNB) or 50 nM strychnine failed to inhibit the ACh-initiated AR, demonstrating that muscarinic AChRs and nAChRs containing alpha9 subunits do not mediate this event. Choline (2.5, 5 and 10 mM), a highly specific but low potency agonist of the alpha7 nAChR initiated AR, with its effect blocked by the nAChR antagonist methyllycaconitine (MLA). ACh (50-400 microM) stimulated a small transient rise in the intracellular Ca2+ in sperm populations loaded with FURA-2, with 200 microM ACh being maximal (146 nM +/- 23 SEM). The nAChR antagonists, alpha-bungarotoxin (alpha-BTX) and MLA, reduced the ACh-initiated Ca2+ rise by 75 and 78%, respectively, demonstrating the majority of the rise is mediated through nAChRs containing alpha7 or alpha9 subunits. Single cell imaging studies using FLUO-3 resolved two patterns of ACh-stimulated Ca2+ increase in the sperm head: 94% of responding sperm displayed a rise (59.6% +/- 5.7 SEM increase from resting fluorescence intensity), returning to resting levels over a period of 2-3 min. The remaining sperm (6%) displayed a sharp spike of Ca2+ ( approximately 1 min; 86% +/- 4.3 SEM change in fluorescence intensity), followed by abrupt loss of fluorescence, a pattern suggestive of AR. A Ca2+ influx in the sperm midpiece appeared to accompany the Ca2+ influx seen in the head. These observations confirm an ionotropic role for nAChRs in sperm function.
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PMID:Acetylcholine causes an increase of intracellular calcium in human sperm. 1642 Dec 12

This study concerns the preparation, physical, and in vitro characterization of two different types of hydroxyapatite (HA) microspheres, which are intended to be used as drug-delivery systems and bone-regeneration matrices. Hydroxyapatite nanoparticles (HA-1 and HA-2) were prepared using the chemical precipitation synthesis with H(3)PO(4), Ca(OH)(2), and a surfactant, SDS (sodium dodecyl sulfate), as starting reagents. The HA powders were dispersed in a sodium alginate solution, and spherical particles were obtained by droplet extrusion coupled with ionotropic gelation in the presence of Ca(2+). These were subsequently sintered to produce HA-1 and HA-2 microspheres with a uniform size and interconnected microporosity. Both powders and microspheres were characterized using FTIR and X-ray diffraction. Moreover, SEM and mercury intrusion porosimetry were used to analyze the microspheres, and TEM was used to analyze the powders. Results showed that pure HA and mixtures of HA/beta-TCP in the nanometer range and needlelike shape were obtained for HA-1 and HA-2 powders, respectively. Neutral Red, scanning electron microscopy and confocal microscopy were used to evaluate the behavior of osteoblastic-like MG-63 cells cultured on HA microspheres surfaces for 7 days. Results showed that good adhesion and proliferation of osteoblasts on the HA microspheres surface. Cells built bridges between adjacent microspheres, forming microspheres-cells clusters in both types of materials.
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PMID:Comparative study of nanohydroxyapatite microspheres for medical applications. 1797 24


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