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M Maitre

Publications and source records attributed to M Maitre.

At least 19 recordsLinked to original sources
PubMed1992

Selective distribution pattern of gamma-hydroxybutyrate receptors in the rat forebrain and midbrain as revealed by quantitative autoradiography.

Using quantitative autoradiography to study the precise distribution of gamma-hydroxybutyrate high-affinity binding sites, the present results showed the heterogeneous localization of these sites in cortical and hippocampal layers and also in some diencephalic and mesencephalic nuclei. In frontal, parietal and temporal cortex, GHB binding sites are generally distributed in three distinct layers. The olfactory system, the amygdala, septum, basal ganglia and substantia nigra also exhibited significant amounts of GHB receptors. In thalamus, the radioactivity was heterogeneously distributed, the highest amounts being in the lateral posterior nucleus. Hypothalamus, cerebellum, colliculi and pons-medulla were apparently devoid of binding sites. This more accurate mapping of GHB high-affinity receptors in rat brain is due to some technical improvements and the use of [3H]GHB of higher specific activity.

Animals↗
PubMed1991

Anti-sedative and anti-cataleptic properties of NCS-382, a gamma-hydroxybutyrate receptor antagonist.

NCS-382 possesses antagonistic properties at gamma-hydroxybutyrate receptor sites. Its effect on the sedative/cataleptic behaviour observed in rats after gamma-hydroxybutyrate administration was investigated. NCS-382 diminished, in a dose-dependent manner, the sedative and/or cataleptic effects of gamma-hydroxybutyrate, as revealed by a variety of sensorimotor tests. These results indicate that the well-known sedative/anaesthetic effects induced by gamma-hydroxybutyrate administration are provoked via stimulation of a specific class(es) of gamma-hydroxybutyrate receptors which exist in the rat brain and which could mediate a local stimulation of opiate synthesis and release.

Animals↗
PubMed1991

Purification and characterization of G proteins from human brain: modification of GTPase activity upon phosphorylation.

Three G proteins from human brain membranes were purified to near homogeneity by conventional techniques including preparative electrophoresis. These G proteins were characterized by their ability to bind GTP, GDP and GTP analogs. Two of these proteins have molecular weights of 50,000 (G50) and 36,000 (G36), as determined on SDS-gels. G36 was ADP-ribosylated by pertussis toxin. Thus, G50 could represent a Gs alpha subunit, whereas G36 could be Gi alpha or Go alpha. G50 was phosphorylated by cAMP dependent protein kinase and protein kinase C. G36 was phosphorylated by a protein kinase independent of calcium and phospholipid, a proteolytic product of protein kinase C, analogous to protein kinase M. Phosphorylation of G36 by this protein kinase induced a dramatic decrease in its GTPase activity. The third G protein, of molecular weight 22,000 probably belongs to the group of monomeric G proteins possessing functional similarities with ras gene products. The regulation of G proteins involving calcium-dependent and independent pathways is delineated.

Adenosine Diphosphate Ribose↗
PubMed1991

Primary dissociated cell culture of embryonic rat metencephalon: presence of GABA in serotonergic neurons.

This study was performed to determine whether neurons, where gamma-aminobutyric acid (GABA) and serotonin (5-HT) coexist, represent neuronal entities which can survive in vitro. In dissociated cultures from 18-day-old embryonic rat metencephalon, it was possible to develop glial and neuronal cells. Among the neurons, some of them, which contain glutamate decarboxylase or are capable of accumulating [3H]GABA are GABAergic; others, containing tryptophan hydroxylase or 5-HT are serotoninergic. By combining radioautography and immunocytochemistry, it was possible to observe neurons where 5-HT and GABA coexist. Cultures might be a suitable model to study the functioning (release or synthesis of both neurotransmitters) of neurons where two classical neurotransmitters coexist.

Animals↗
PubMed1991

Isolation of human brain protein kinase C: evidence for kinase C catalytic fragment modulating G protein-GTPase activity.

Protein kinase C from human brain was isolated and characterized. A protein kinase M like kinase of molecular weight 63 kDa was also partially purified and identified by its immunological properties similar to those of kinase C. The kinase M like kinase activity, devoid of Ca2+ and phospholipids dependency, was also characterized by its inhibition profile by several ligands. Since this kinase phosphorylates a G protein (M.W. 36 kDa) and decreases its GTPase activity which could be restored by alkaline phosphatase, it is concluded that this kinase M like kinase could interact with G protein mediated events of neuronal responses.

Alkaline Phosphatase↗
PubMed1991

Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study.

The modification of dopamine release and accumulation induced by gamma-hydroxybutyrate (GHB) was studied using both striatal slices and in vivo microdialysis of caudate-putamen. GHB inhibited dopamine release for approximately 5-10 min in vitro, and this was associated with an accumulation of dopamine in the tissue. Subsequently, there was an increase in dopamine release. In the microdialysis experiments, low doses of GHB inhibited dopamine release, whereas higher doses strongly increased release; the initial decrease seen in slices could not be detected in vivo. Thus, GHB had a biphasic effect on the release of dopamine: An initial decrease in the release of transmitter was followed by an increase. A time-dependent biphasic effect was observed when GHB was added to brain slices, and a dose-dependent biphasic effect was seen in dialysate after systemic administration of GHB. Naloxone blocked GHB-induced dopamine accumulation and release both in vitro and in vivo. GHB also increased the release of opioid-like substances in the striatum. A specific antagonist of GHB receptors completely blocked both the dopamine response and the release of opioid-like substances. These data suggest that GHB increases dopamine release via specific receptors that may modulate the activity of opioid interneurons.

Administration, Topical↗
PubMed1991

Isolation of monoaminergic synaptosomes from rat brain by immunomagnetophoresis.

Monoaminergic synaptosomes have been isolated and purified from rat brain by immunomagnetophoresis. This novel technique uses magnetic beads to which Protein A is bound. Noradrenergic, dopaminergic, and serotonergic synaptosomes (previously cell-surface labelled with anti-dopamine-beta-hydroxylase, anti-tyrosine hydroxylase, and anti-tryptophan hydroxylase, respectively) may be isolated in a highly purified state. The synaptosomal subpopulations are recovered in a viable metabolic state and show glucose-stimulated respiration and Ca2(+)-dependent neurotransmitter release. A novel subtype of dopamine-beta-hydroxylase was found in dopaminergic terminals. No evidence for glutamate corelease from monoaminergic synaptosomes was obtained.

Animals↗
PubMed1991

Tryptophan hydroxylase synthesis is induced by 3',5'-cyclic adenosine monophosphate during circadian rhythm in the rat pineal gland.

Tryptophan hydroxylase in the rat pineal gland undergoes diurnal rhythmic activity. Rat pineal glands exhibit increased tryptophan hydroxylase activity when incubated with a cyclic AMP analogue in vitro. Cyclic AMP-dependent protein kinase phosphorylates tryptophan hydroxylase, purified from rat brain, without any modification of its enzyme activity under our experimental conditions. Actinomycin D or cycloheximide decreases the stimulating effect of the cyclic AMP analogue on pineal tryptophan hydroxylase activity. Incubation of pineal glands in the presence of [35S]methionine showed a cyclic AMP-induced increase in tryptophan hydroxylase synthesis. These results explain the circadian rhythm of tryptophan hydroxylase activity in the rat pineal gland and suggest that the regulation of tryptophan hydroxylase expression by cyclic AMP occurs probably either at the translational level or via transient expression of a transcriptional regulatory element.

Animals↗
PubMed1990

Effects of phospholipases, proteases and neuraminidase on gamma-hydroxybutyrate binding sites.

gamma-Hydroxybutyric acid (GHB) is a natural compound of mammalian brain synthesized from GABA. The characteristics of its synthesis, transport, release, distribution and turnover, in addition to the presence of a high affinity binding site for this substance in brain are in favor of a modulator role for GHB. The effects of hydrolytic enzymes on the specific binding capacity of GHB have been studied in the present work. Phospholipases A2 and C, neuraminidase and Pronase markedly decrease GHB binding to crude synaptosomal membranes from rat brain. This effect is time and enzyme concentration dependent. Trypsin, under the conditions employed, is less active. The inhibitory effects of phospholipases is correlated with phospholipid hydrolysis. Lysophospholipids, in the absence of bovine fatty acid free serum albumin partially inhibit GHB binding. The action of neuraminidase has been followed by sialic acid release and modifications of the ganglioside profile. The effects of phospholipase C and of neuraminidase are completely different to those on GABA binding sites. These results represent further data concerning the molecular existence of specific GHB binding sites on rat brain membranes.

Animals↗
PubMed1990

Trans-gamma-hydroxycrotonic acid binding sites in brain: evidence for a subpopulation of gamma-hydroxybutyrate sites.

Trans-gamma-hydroxycrotonate (THCA), a compound naturally present in rat brain, possesses high-affinity binding sites with a heterogeneous distribution which are superimposable with those for gamma-hydroxybutyrate (GHB). Binding studies of THCA on rat brain membranes revealed two binding components, one of high affinity (Kd1, 7 nM, Bmax1 42 fmol/mg protein) and the other of low affinity (Kd2, 2 microM, Bmax2 13 pmol/mg protein). Displacement curves of [3H]THCA by THCA and GHB or of [3H]GHB by THCA are in favour of the existence of a specific high affinity site for THCA. Quantitative autoradiography with image analysis of [3H]THCA binding in rat brain slices indicated that [3H]THCA high affinity binding was displaced at a lower potency by GHB. THCA showed also some selectivity in displacing [3H]GHB from its high affinity binding site (Kd = 95 nM). This mutual overlap favours a subpopulation of GHB receptors, which have THCA as a natural ligand, showing partial agonistic properties compared to GHB. The functional significance of this result remains unknown.

Animals↗
PubMed1990

Increased gamma-hydroxybutyric acid receptors in thalamus of a genetic animal model of petit mal epilepsy.

The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epileptic controls using [3H]GHB autoradiography. [3H]GHB receptor binding was increased 40-60% in lateral thalamic nuclei of the epileptic animals. Kinetic analysis showed that the increase in the binding was due to an increase in density of low affinity GHB binding sites in the epileptic animals. Given the ability of GHB to produce petit mal-like seizures when administered to animals, and the fact that the SWDs in the Wistar rat model seem to emanate from lateral thalamus, these data raise the possibility that GHB-mediated mechanisms may play a role in the pathogenesis of petit mal seizures.

Animals↗
PubMed1990

A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties.

Administration of gamma-hydroxybutyrate (GHB) to animals induces electroencephalographic and behavioral changes that resemble petit-mal seizures. Furthermore, these GHB-induced electroencephalogram-behavioral changes can be blocked by anticonvulsant drugs, which are specific in their action against petit-mal seizures. These effects of GHB on electroencephalogram and behavior may well be due to an effect of exogenously administrated GHB on GHB-mediated systems in the brain. GHB has many properties of a neuromodulator including the existence of receptors with a specific affinity for this compound. A synthetic structural analog of GHB, NCS-382, possessed anticonvulsant activity against several animal models of seizure and, in particular, against that induced by GHB administration. NCS-382 was also shown to be an antagonist at GHB receptor sites and blocked the neuropharmacologic effects induced in the striatum and hippocampus by GHB administration. In particular, NCS-382 inhibited the increase in cGMP levels and in inositol phosphate turnover induced by GHB in hippocampus. Furthermore, in vivo dialysis demonstrated that NCS-382 blocked the increased release of dopamine in striatum after GHB administration in vivo. Thus, this ligand appears to be the first described antagonist substance for GHB receptor(s). These results suggest that NCS-382 may represent a harbinger for a new class of anticonvulsant drugs that most probably act by modifying the endogenous GHB system.

Animals↗
PubMed1989

The immunolysis, isolation, and properties of subpopulations of mammalian brain synaptosomes.

Five subpopulations of mammalian brain synaptosomes can be selectively damaged by complement-mediated immunolysis employing antibodies to specific surface markers for each subpopulation. This allows the size of these subpopulations to be estimated. Employing antibodies alone, it has proved possible to isolate three of these subpopulations in very pure preparations which are metabolically viable. The immunoaffinity technique involved (immunomagnetophoresis) uses magnetic microspheres and produces mg (protein) quantities of synaptosomes.

Animals↗
PubMed1989

Formal demonstration of the phosphorylation of rat brain tryptophan hydroxylase by Ca2+/calmodulin-dependent protein kinase.

Tryptophan hydroxylase is activated in a crude extract by addition of ATP and Mg2+. This activation is reversible and requires in addition both Ca2+ and calmodulin. Thus, phosphorylation by an endogenous calmodulin-dependent protein kinase has long been suspected. Now that we have prepared a specific polyclonal antibody to rat brain tryptophan hydroxylase, we have been able to prove that this hypothesis is correct. After incubation of purified tryptophan hydroxylase with Ca2+/calmodulin-dependent protein kinase together with [gamma-32P]ATP, Mg2+, Ca2+, and calmodulin, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotting of the enzymes onto nitrocellulose sheets, we could label the band of tryptophan hydroxylase by the antiserum and the peroxidase technique and show by autoradiography that 32P was incorporated into this band. By measuring the radioactivity, we calculated that about 1 mol of phosphate was incorporated per 8 mol of subunits of the enzyme (2 mol of native enzyme). Because the concentration of ATP which we employed (50 microM) gives about half-maximal activation in crude extract compared to saturating ATP conditions (about 1 mM), this result indicates that the incorporation of at least 1 mol of phosphate/mol of tetramer of native tryptophan hydroxylase is required for maximal activation.

Adenosine Triphosphate↗
PubMed1989

Gamma-hydroxybutyrate stimulation of the formation of cyclic GMP and inositol phosphates in rat hippocampal slices.

The presence of gamma-hydroxybutyrate (GHB) (300-600 microM) in the incubation medium of rat hippocampal slices led to an increase of intracellular cyclic GMP and inositol phosphates. This phenomenon is dependent on the time and the dose of GHB used and might be the result of the stimulation of GHB receptor sites which are abundant in rat hippocampus. The increase of cyclic GMP and inositol phosphates is blocked by some anticonvulsants and opiate antagonists. These results seems to indicate that, like many substances inducing epileptic phenomena, GHB provokes neuronal depolarization in hippocampus which is accompanied by formation of cyclic GMP and inositol phosphates. The effect of opiate antagonists can be explained by the possible implication of an opiate synapse which mediates GHB effects in rat hippocampus.

Animals↗
PubMed1987

3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone.

An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg gamma-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP.

Animals↗