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

We have studied the effect of increasing concentrations of isoflurane on high- and low-affinity uptake of L-glutamate using synaptosomes from rat cerebral cortex. In the high-affinity uptake range, 0.5% isoflurane had no effect on uptake velocity, while 1.5% and 3.0% isoflurane caused an increase in mean Vmax to 131 (SEM 54) and 210 (103)% of control, respectively. There was no significant change in the K(m) value. Vmax and K(m) values for low-affinity uptake of L-glutamate were unchanged by 1.5% isoflurane. These results provide evidence for an isoflurane-induced increase in high-affinity uptake of glutamate into presynaptic terminals. This effect may contribute to a reduction of transmitter in the synaptic cleft and thereby decreased excitatory synaptic transmission.
 ...
PMID:Isoflurane increases the uptake of glutamate in synaptosomes from rat cerebral cortex. 905 5

The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8) was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no significant effect on the depressant potency of AP4. Under control conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary afferent terminals presynaptic to motoneurones as well as in pathways via interneurones. These results are consistent with the presence of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These receptors appear to be activated by interstitial glutamate tonically present in the present preparations.
 ...
PMID:Antagonism of mGlu receptors and potentiation of EPSCs at rat spinal motoneurones in vitro. 917 9

Ontogenesis of both vagal control of heart rate and the baroreceptor vagal reflex were evaluated in rats at postnatal ages (P) of 5/6, 10, 15, 20, 25 and >>42 days anaesthetised with urethane (1.5 g/kg). Between P5/6 and P25 heart rate rose from 372 +/- 12 to 448 +/- 20 beats per minute and mean arterial pressure increased from 33.9 +/- 3.1 to 74.59 +/- 3.25 mm Hg (mean +/- SEM, n = 7 and 11 respectively). Cardiac vagal tone was absent at P10 but significant at P20 (P < 0.05) as revealed with atropine (0.5-1 mg/kg i.v.). Baroreceptor cardiac reflex sensitivity, tested with phenylephrine (10-50 microg/kg i.v.), was attenuated significantly in P10-20 rats compared with P5/6, P25 and mature animals. In P14-17 rats stimulation of neurones in either the solitary tract or ambiguual nuclei, by microinjection of L-glutamate (100-200 pmol), evoked an atropine-sensitive bradycardia indicating a functional integrity of central and peripheral efferent pathways mediating the baroreceptor reflex. Thus, the baroreceptor vagal reflex is functional in P5/6 rats but becomes attenuated between P10-P20, which is coincident with the maturational rise in arterial pressure.
 ...
PMID:Changes in baroreceptor vagal reflex performance in the developing rat. 921 10

The 5-HT3 receptor is a ligand-gated ion channel with significant structural similarity to the nicotinic acetylcholine receptor. Several regions that form the ligand binding site in the nicotinic acetylcholine receptor are partially conserved in the 5-HT3 receptor, presumably reflecting the conserved signal transduction mechanism. Specific amino acid differences in these regions may account for their distinct ligand recognition properties. Using site-directed mutagenesis, we have replaced one of these residues, glutamate 106 (E106), with aspartate (D), asparagine (N), alanine (A) or glutamine (Q) and characterized the ligand-binding and electrophysiological properties of the mutant receptors after transient expression in HEK-293 cells. The affinity for the selective 5-HT3 receptor antagonist [3H]GR65630 was decreased 14-fold in the mutant E106D (Kd = 3.69 +/- 0.32 nM) when compared to wildtype (WT, E106) 5-HT3 receptor (0.27 +/- 0.03 nM), while the affinity for E106N was unchanged (0.42 +/- 0.07 nM, means +/- SEM, n = 3-10). Decreased affinities for both E106D and E106N were observed for the antagonists granisetron, ondansetron and renzapride and for the agonists 5-HT (130- and 30-fold) and 2-methyl-5-HT (250- and 20-fold), respectively. Both mutants still formed 5-HT-activatable ion channels, but the high Hill coefficient of the concentration effect curves in wildtype (2.0) was decreased to unity in both cases. The EC50 of 5-HT was increased seven-fold in E106N (8.7 microM) when compared to wildtype (1.2 microM), but unchanged in E106D, and the potency of the antagonist ondansetron for both mutants was decreased. E106A and E106Q expressed poorly preventing a detailed characterization. These data suggest that E106 contributes to the ligand-binding site of the 5-HT3 receptor and may form an ionic or hydrogen bond interaction with the primary ammonium group of 5-HT.
 ...
PMID:Analysis of the ligand binding site of the 5-HT3 receptor using site directed mutagenesis: importance of glutamate 106. 922 89

In this study we sought to determine the role of the paraventricular nucleus of the hypothalamus (PVN) in modulating respiratory output. Experiments were performed in urethane anesthetized, vagotomized and mechanically ventilated Wistar rats. Electromyographic activity of the diaphragm (D[EMG]) was recorded and used to define the respiratory effects of PVN stimulation. The ventilation rate and volume were pre-adjusted so that baseline activity was 30% of the activity observed upon addition of 7% CO2 in O2. Microinjection of L-glutamate (4 nmol, 100 nl) into the PVN produced an increase in peak D(EMG), and an increase in frequency of D(EMG) discharge. Changes in respiratory timing were mainly due to shortening of expiratory time (0.66 +/- 0.06 s vs. 0.90 +/- 0.10 s; mean +/- SEM; P < 0.05), while inspiratory time was less affected (0.48 +/- 0.04 vs. 0.51 +/- 0.04 s; P > 005). The rate of rise of D(EMG) increased by 101 +/- 28% from the baseline (P < 0.05). In addition, neuroanatomical tracing studies suggest the presence of direct connection between PVN and phrenic motoneurons. The results indicate that PVN neurons participate in regulation of breathing activity and in coordination of cardiovascular and respiratory functions.
 ...
PMID:The paraventricular nucleus of the hypothalamus influences respiratory timing and activity in the rat. 930 87

We have examined the binding of the local anaesthetic agent [3H]amethocaine to rat cerebrocortical membranes. All studies were performed in Tris buffer 50 mmol litre-1 at pH 7.4. Bound and free radioligand were separated by rapid vacuum filtration. [3H]Amethocaine binding at room temperature was dose-dependent and saturable, with mean Kd and Bmax values of 153 (SEM 18) nmol litre-1 and 9.4 (1.6) pmol/mg protein, respectively. [3H]Amethocaine binding was displaced in a dose-dependent manner (pIC50) by unlabelled amethocaine (6.89), procaine (5.20), lignocaine (3.46) and prilocaine (2.81). Ropivacaine and bupivacaine did not produce 50% displacement at the highest concentrations used (10(-4) and 10(-3) mol litre-1, respectively). We examined the nature of the binding site further with a range of ion channel antagonists (nifedipine, verapamil, diltiazem, omega-conotoxin, tetrodotoxin, tetraethylammonium and 4-aminopyridine) and ion channel coupled receptor ligands (L-glutamate, MK801, GABA, glycine and nicotine). With the exception of tetraethylammonium (pIC50 3.07) and 4-aminopyridine (pIC50 3.68), all non-anaesthetic agents failed to displace [3H]amethocaine. Collectively our data suggest that it is unlikely that there is a single target site for all local anaesthetic agents.
 ...
PMID:Studies on the binding of [3H]amethocaine to rat cerebrocortical membranes. 938 74

The actions of peptidic toxins that work as Ca2+-channel antagonists were investigated on neostriatal glutamatergic transmission. Both intracellularly recorded excitatory postsynaptic potentials (EPSPs) and extracellularly recorded population spikes (PS) evoked by afferent stimulation were evaluated in the presence of 10 microM bicuculline. Percentage of block (mean +/- SEM; n = 4) for these events (EPSP and PS, respectively) was: omega-AgTxIVA (100-200 nM): 35 +/- 2 and 54 +/- 4%; omega-CgTxGVIA (1 microM): 37 +/- 3 and 63 +/- 6%; omega-CgTxMVIIC (500 nM): 40 +/- 4 and 50 +/- 2%; and calciseptine (500 nM): 5 +/- 4 and 9 +/- 6%. When given together, toxins had additive effects. The calciseptine effects were nonsignificant. The toxins were also tested on Ca2+-dependent random synaptic responses induced by 100 microM 4-AP. Each toxin reduced the frequency of spontaneous EPSPs by more than 60% (n = 2). The summed actions of individual toxins yields more than 100% block (superadditivity); suggesting that several terminals may possess more than one channel type. The reduction in frequency was not accompanied by a reduction in amplitude confirming that toxins' actions were presynaptic. It is concluded that at least three different Ca2+-channel subtypes are involved in glutamate release in neostriatal afferents: N-type, P/Q-type, and a type resistant to the toxins used. The L-type Ca2+-channel had little, if any, participation.
 ...
PMID:Ca2+-channels involved in neostriatal glutamatergic transmission. 957 Jul 23

Block copolymers consisting of poly(gamma-benzyl L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene oxide) (PEO) as the hydrophilic block were synthesized and characterized. Core-shell type nanoparticles of the block copolymers (abbreviated as GE) were prepared by the diafiltration method. The particle size diameter obtained by dynamic light scattering of GE-1 (PBLG content: 60.5 mol%), GE-2 (PBLG content: 40.0 mol %), GE-3 (PBLG content: 124.4 mol %) copolymer was 309.9 +/- 160.9, 251.9 +/- 220.6 and 200.5 +/- 177.1nm, respectively. The shape of the nanoparticles by SEM or TEM was almost spherical. The critical micelle concentration of the block copolymers obtained by fluorescence spectroscopy was dependent on the chain length of hydrophobic PBLG. The micelle structure of the copolymers nanoparticle was very stable against sodium dodecyl sulfate. Clonazepam (CZ) was loaded onto the core part of the nanoparticle as the crystalline state. Release of CZ from the nanoparticles in vitro was dependent on the drug loading contents and PBLG chain length.
 ...
PMID:Clonazepam release from core-shell type nanoparticles in vitro. 968 14

Immunocytological localization of omega-agatoxin IVA (omega-aga IVA)-sensitive Ca2+ channels involved in glutamate release from growth cones of cultured rat dorsal root ganglion (DRG) neurons was studied with field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The omega-aga IVA-sensitive Ca2+ channels were visualized by labeling with immuno-gold particles (30 nm). FE-SEM and TEM images showed that immuno-gold particles were present in the area of growth cones as well as somata, and generally absent on neurite stem and fibroblasts. TEM images of vertical ultra-thin sections showed that the immuno-gold particles were present on the surface of the plasma membrane. Since the gold particles indicate the immunological presence of omega-aga IVA-sensitive Ca2+ channels, the Ca2+ channels involved in transmitter release are present on growth cones before making synapse formation.
 ...
PMID:Visualization of calcium channels involved in transmitter release from neuronal growth cones. 971 82

We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O2 supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n = 8), 21% O2 (n = 8), and 100% O2 groups (n = 8). The hypoxaemic group was mechanically ventilated with 12-18% O2 adjusted to achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%, mean +/- SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p = 0.044 and p = 0.055, respectively) than during resuscitation with 21% O2 or 100% O2, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na+,K+-ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups (p = 0.30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O2. Resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.
 ...
PMID:Cerebral excitatory amino acids and Na+,K+-ATPase activity during resuscitation of severely hypoxic newborn piglets. 973 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>