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)

The electrical properties of neurones within the ventromedial hypothalamic nucleus of the rat were studied in an in vitro slice preparation, using conventional intracellular recording techniques. A detailed analysis of 36 intracellular recordings appeared to suggest 3 cell types, based on membrane capacitance and resistance characteristics, confirming previous reports of a diversity of cell types within this nucleus. The responsiveness of each cell type to exogenously-applied baclofen and somatostatin was also investigated. The inhibitory responses to both of these drugs were concentration-related (over the range 100 nM to 1 microM), tetrodotoxin-resistant and consisted of a membrane hyperpolarization (mean +/- SEM = 6.7 +/- 1 and 10.7 +/- 1 mV for 1 microM somatostatin and baclofen, respectively) and an associated reduction in the firing frequency of spontaneously active cells. These agonist-evoked responses probably represented direct postsynaptic actions but they were not restricted to any single type of cell. Evidence for an additional presynaptic effect of baclofen was also obtained. Responses to baclofen were extremely robust and readily quantifiable, whereas those to somatostatin showed pronounced long-lasting desensitization, which was particularly marked a larger concentrations. These data support previous contentions, based on in vivo studies, that somatostatin and GABA are likely to participate in the control of complex functions by the ventromedial hypothalamic nucleus.
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PMID:The effect of baclofen and somatostatin on neuronal activity in the rat ventromedial hypothalamic nucleus in vitro. 134 9

To elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling, genotype rol/rol), an experimental neurologic mutant mouse, we studied the physiological characteristics of neurons of the globus pallidus (GP) in rolling, comparing them with those of the behaviorally normal heterozygotes (+/rol) and normal controls (+/+). Forty-nine units in rolling, 41 in heterozygotes and 48 in controls were recorded under urethane anesthesia. The group mean of the interspike interval (ISI) of the spontaneous unit discharges was significantly shorter in rolling (42.2 +/- 2.6 msec, mean +/- SEM) than that of controls and of heterozygotes (55.4 +/- 2.4 msec, P < 0.001 and 50.4 +/- 2.6 msec, P < 0.05, respectively), indicating a significantly higher rate of spontaneous unit activity in the GP of rolling. In the controls and heterozygotes, about 60% of the GP neurons responded to striatal (ST) electrical stimulation with a predominantly inhibitory response, whereas a significantly smaller number of the GP neurons (22%, P < 0.001) exhibited inhibitory responses in rolling. The positive field potentials recorded in the GP evoked by ST stimulation were significantly smaller in amplitude in rolling (1.04 +/- 0.10 mV, mean +/- SEM) than that of the controls and heterozygotes (1.78 +/- 0.15 mV, P < 0.001 and 1.97 +/- 0.17 mV, P < 0.001, respectively). These results are in agreement with our previously reported findings of increased glucose metabolism and reduced concentration of GABA in the GP and substantia nigra pars reticula (SNr) in rolling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Striatal dysfunction in Rolling mouse Nagoya: an electrophysiological study. 146 20

Interneurons from the CA1 lacunosum-moleculare (L-M) region were isolated by trypsin-hyaluronidase treatment and mechanical trituration of the L-M. Interneurons isolated in this manner were multipolar with several dendritic processes and could be distinguished from CA1 pyramidal neurons. The properties of a low-threshold transient (LTT) Ca2+ current were investigated using whole-cell voltage-clamp techniques. The activation threshold of the LTT Ca2+ current was -60 mV, and the peak current, 100 +/- 9 pA (mean +/- SEM; n = 15), was observed at -30 mV. Ca2+ was the predominant charge carrier because the current was not affected by tetrodotoxin and was abolished in Ca(2+)-free external solution. Steady state inactivation was observed when the holding potential was positive to -100 mV, and the current was half-inactivated at -84 mV. Complete inactivation occurred at a holding potential of -60 mV. The time-to-peak of the current was highly voltage dependent and ranged from 10 msec at -60 mV to 4 msec at 0 mV. The time constant of inactivation was also voltage dependent and ranged from 27 msec at -60 mV to 12 msec at greater than -30 mV. Recovery from inactivation to 90% of maximum current occurred within 200 msec. L-M interneurons receive synaptic inputs from the septum that release ACh or GABA and from the raphe nuclei that release 5-HT. Carbachol, a nonhydrolyzable cholinergic agonist, and 5-HT quickly and reversibly increased the amplitude of the LTT Ca2+ current. Carbachol's actions were blocked by atropine, indicating that this effect was mediated by muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-threshold transient calcium current in rat hippocampal lacunosum-moleculare interneurons: kinetics and modulation by neurotransmitters. 167 22

1. The C elevation of the compound action potential (CAP) was recorded with suction electrodes from dorsal roots of rats at 25 degrees C and toads (Bufo bufo) at 10 degrees C. The C fibre CAP had a conduction velocity of 0.5 +/- 0.07 SE M per sec (N = 10) and 0.25 +/- 0.04 M per sec (N = 8) in the rat and toad nerves respectively. 2. The depressant effect of applied drugs on the amplitude of the C fibres CAP was measured. Nerves from both species had similar sensitivities to GABA. EC50 5.0 microM +/- 0.5 SEM (N = 3) and 5.5 microM +/- 1.4 (N = 3) for the rat and toad respectively. Maximum depressant effects of GABA produced in rat and toad nerves were 35% +/- 5 SEM and 17% +/- 2.5 respectively. 3. In five out of ten of the rat nerves tested kainate had a clear depressant effect (maximum 36% +/- 4.3 SEM, EC50 6.8 microM +/- 0.9 SEM, N = 3) on the C fibre CAP. Kainate, at concentrations from 100 to 500 microM, had no effect on seven toad nerves. 4. Toad nerves were about 100 times less sensitive, than rat nerves, to capsaicin (ED50 values 430 microM +/- 190 SEM and 0.7 microM +/- 0.2 respectively, N = 4). 5. The similar sensitivity of nerves in both species to GABA and differing sensitivities to kainate and capsaicin suggests that amphibian C fibres specifically lack sensitivity to capsaicin and kainate.
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PMID:Comparison of the capsaicin- and amino acid-sensitivity of dorsal root C fibres in the rat and the toad. 168 27

Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1-100 mumol/l) was applied cumulatively and EC50 and IC50 values measured from individual concentration-response curves. Blockade of 5-HT responses by the 3-indazole carboxamide, BRL 43694, was investigated and compared with the blocking action of metoclopramide. BRL 43694 was a selective antagonist of 5-HT responses. A concentration of 10 nmol/l BRL 43694, which nearly abolished the depolarization and reduction of the C spike evoked by 5-HT (100 mumol/l), had no effect on similar responses evoked by DMPP (100 mumol/l) or GABA (100 mumol/l). Blockade of 5-HT responses by BRL 43694 (0.3 nmol/l) was slow in onset, a plateau blockade occurring after equilibrium of tissue with antagonist for 2 to 3 h. Metoclopramide induced a blockade of rapid onset. The maximal blockade was apparent within 30 min of application. Full recovery in the responsiveness of the tissue to 5-HT was observed within 30 min of washing out metoclopramide. BRL 43694 at concentrations of 0.3, 1, 3 and 10 nmol/l caused a progressive rightward shift of the concentration-response curves to 5-HT. At the highest concentration of antagonist, there was some depression of the maximal 5-HT response. The apparent pA2 estimated from the Schild equation was 10.03 +/- 0.09 (mean +/- SEM, n = 20) against 5-HT depolarization and 10.31 +/- 0.1 against C spike reduction. Schild plots had slopes not significantly different from 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of the effects of 5-hydroxytryptamine on the rabbit isolated vagus nerve by BRL 43694 and metoclopramide. 216 21

The characteristics of benzodiazepine binding sites (affinity, number heterogeneity) were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. 3H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives (GABA, catecholamines, hydroxy-indols) were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. We observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, (7.48 +/- 1.7 to 17.24 +/- 1.7 nM, P less than 0.01), (m +/- SEM) and an increase in % of type I binding sites (30 +/- 4.2 to 42 +/- 2.5, P = 0.01). Among neurotransmitters, only norepinephrine differed significantly between controls and suicides (11.34 +/- 1.9 to 24.34 ng/g tissue, P = 0.02).
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PMID:Benzodiazepine receptor and neurotransmitter studies in the brain of suicides. 289 3

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)--epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)--temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (mumol/g protein, mean +/- SEM): glutamate--spiking 109.8 +/- 1.8, nonspiking 87.4 +/- 2.0 (p less than 0.001); aspartate--spiking 15.2 +/- 0.9, nonspiking 12.2 +/- 0.5 (p less than 0.05); GABA--spiking 15.0 +/- 1.0, nonspiking 13.9 +/- 1.4 (NS); taurine--spiking 14.5 +/- 0.8, nonspiking 12.2 +/- 0.8 (NS); and glycine--spiking 11.5 +/- 0.8, nonspiking 7.4 +/- 0.6 (p less than 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.
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PMID:Excitatory amino acids are elevated in human epileptic cerebral cortex. 336 74

Serum levels of GABA (gamma-aminobutyric acid)-like activity were measured by a radioreceptor assay in 22 healthy subjects and 170 patients with liver diseases. Levels were within normal limits (mean +/- SEM in healthy controls 0.52 +/- 0.04 mumol/l; range 0.2-0.8 mumol/l GABA equivalents) in most patients with uncomplicated acute viral hepatitis, compensated chronic hepatitis, and primary biliary cirrhosis (PBC). In 96% of patients with compensated (non-PBC) cirrhosis levels were slightly high (1.5 +/- 0.06 mumol/l). In 4 patients with decompensated cirrhosis but without hepatic encephalopathy (range 3.0-6.4 mumol/l) and in most of 26 patients with overt hepatic encephalopathy due to acute or chronic hepatocellular failure (range 2.3-18.0 mumol/l) levels were very high. Levels did not correlate closely with the clinical stage of hepatic encephalopathy or with arterial plasma ammonia concentrations. particularly high levels were detected in patients with cirrhosis 12-16 h after gastrointestinal haemorrhages. These findings are compatible with the hypothesis that the GABA neurotransmitter system is involved in the pathogenesis of hepatic encephalopathy in man.
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PMID:Serum levels of gamma-aminobutyric-acid-like activity in acute and chronic hepatocellular disease. 613 47

Five enzymes involved in glutamic acid, GABA, and catecholamine metabolism were measured in epileptic human brain. Electrocorticographically defined areas of focal spiking were compared with samples from surrounding nonspiking cortex. Comparative enzyme activities were as follows (mumol/h/g wet wt): glutamic acid dehydrogenase (GDH)--spiking 135.77 +/- 10.22 (mean +/- SEM), nonspiking 118.58 +/- 9.42 (p less than 0.001, N = 17); glutamic acid decarboxylase--spiking 10.63 +/- 0.95, nonspiking 9.96 +/- 1.10 (NS, N = 13); GABA-aminotransferase--spiking 36.49 +/- 1.05, nonspiking 36.46 +/- 1.48 (NS, N = 12); glutamine synthetase--spiking 96.94 +/- 3.81, nonspiking 96.52 +/- 4.10 (NS, N = 20); and tyrosine hydroxylase (TH; nmol/h/g)--spiking 16.23 +/- 2.39, nonspiking 10.67 +/- 1.95 (p less than 0.001, N = 14). Increased activity of GDH and TH may prove useful to characterize further areas of active spiking in human focal epilepsy.
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PMID:Enzyme changes in actively spiking areas of human epileptic cerebral cortex. 614 16

It was investigated that the cerebral blood flow (CBF) decrease response elicited by chemical stimulation of the caudal ventrolateral medullary depressor area (VLDA) is mediated via the rostral ventrolateral medullary pressor area (VLPA) and the cervical sympathetic nerve. The CBF was determined by radiolabeled microsphere technique in urethane (1.1-1.5 g.kg-1, i.p.) anesthetized Wistar rats. (i) Microinjection of L-glutamate (1.7 nmol) into the VLDA produced a significant (P < 0.01) decrease in CBF from 64 +/- 9 (mean +/- SEM) to 48 +/- 9 ml.min-1.(100 g)-1 and a significant (P < 0.01) increase in cerebrovascular resistance (CVR) from 1.7 +/- 0.2 to 2.4 +/- 0.4 mmHg per [ml.min-1.(100 g)-1] in the cerebral cortex ipsilateral to the stimulated VLDA side (n = 9). (ii) After cervical sympathectomy, L-glutamate was unilaterally microinjected into the VLDA. The CBF and CVR did not change significantly (n = 10). (iii) After depression of the VLPA neurons with muscimol (GABA agonist), L-glutamate was unilaterally microinjected into the VLDA. The CBF and CVR did not change significantly (n = 14). These results suggest that the pathway from the VLDA to control cerebral vessels may be mediated via the VLPA and the cervical sympathetic nerves.
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PMID:Cerebral vasoconstrictive response produced by chemical stimulation of the caudal ventrolateral medullary depressor area is mediated via the rostral ventrolateral medullary pressor area and the cervical sympathetic nerves. 783 81


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