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M De Murtas

Publications and source records attributed to M De Murtas.

16 recordsLinked to original sources
PubMed1995

Vulnerability of medium spiny striatal neurons to glutamate: role of Na+/K+ ATPase.

In Huntington's disease neuronal degeneration mainly involves medium-sized spiny neurons. It has been postulated that both excitotoxic mechanisms and energy metabolism failure are implicated in the neuronal degeneration observed in Huntington's disease. In central neurons, > 40% of the energy released by respiration is used by Na+/K+ ATPase to maintain ionic gradients. Considering that impairment of Na+/K+ ATPase activity might alter postsynaptic responsivity to excitatory amino acids (EAAs), we investigated the effects of the Na+/K+ ATPase inhibitors, ouabain and strophanthidin, on the responses to different agonists of EAA receptors in identified medium-sized spiny neurons electrophysiologically recorded in the current- and voltage-clamp modes. In most of the cells both ouabain and strophanthidin (1-3 microM) did not cause significant change in the membrane properties of the recorded neurons. Higher doses of either ouabain (30 microM) or strophanthidin (30 microM) induced, per se, an irreversible inward current coupled to an increase in conductance, leading to cell deterioration. Moreover, both ouabain (1-10 microM) and strophanthidin (1-10 microM) dramatically increased the membrane depolarization and the inward current produced by subcritical concentrations of glutamate, AMPA and NMDA. These concentrations of Na+/K+ ATPase inhibitors also increased the membrane responses induced by repetitive cortical activation. In addition, since it had previously been proposed that dopamine mimics the effects of Na+/K+ ATPase inhibitors and that dopamine agonists differentially regulate the postsynaptic responses to EAAs, we tested the possible modulation of EAA-induced membrane depolarization and inward current by dopamine agonists. Neither dopamine nor selective dopamine agonists or antagonists affected the postsynaptic responses to EAAs. Our experiments show that impairment of the activity of Na+/K+ ATPase may render striatal neurons more sensitive to the action of glutamate, lowering the threshold for the excitotoxic events. Our data support neither the role of dopamine as an ouabain-like agent nor the differential modulatory action of dopamine receptors on the EAA-induced responses in the striatum.

Animals↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission.

Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug.

Adenosine↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents.

GP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release.

Animals↗
PubMed1992

Chronic neuroleptic treatment: D2 dopamine receptor supersensitivity and striatal glutamatergic transmission.

We studied the in vitro electrical activity of rat neostriatal neurons following chronic neuroleptic treatment. In haloperidol-treated rats, unlike naive animals, activation of neostriatal D2 dopamine receptors induced a potent presynaptic inhibition of glutamate-mediated excitatory synaptic potentials. Haloperidol treatment did not affect the intrinsic membrane properties of the neostriatal neurons. Pre- and postsynaptic physiological responses to direct and indirect gamma-aminobutyric acid (GABA)-ergic and cholinergic agonists were not affected by chronic haloperidol treatment. These findings suggest that movement disorders induced by chronic neuroleptic treatment may result, at least in part, from a hypersensitivity of presynaptic D2 dopamine receptors regulating the release of glutamate.

Aging↗
PubMed1991

Involvement of GABA systems in feedback regulation of glutamate-and GABA-mediated synaptic potentials in rat neostriatum.

1. Neostriatal neurones were recorded intracellularly from a rat corticostriatal slice preparation. Depolarizing postsynaptic potentials (DPSPs) were evoked by either cortical or intrastriatal stimulation. 2. Kynurenic acid (600 microM), an antagonist of excitatory amino acids, reduced the cortically-evoked DPSPs by 88% while the intrastriatally evoked potentials were reduced by 48%. Bicuculline (100 microM) produced only a slight inhibition of the cortically evoked DPSPs (12%), but clearly depressed intrastriatal potentials (52%). 3. The effects of (-)-baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, were studied on the cortically evoked DPSPs. In all the tested neurones (-)-baclofen, added to the superfusion medium, caused a concentration-dependent decrease of these potentials (half-maximal effect (EC50) = 800 nM). This effect was not affected by bicuculline. (-)-Baclofen did not change the membrane potential, the input resistance, current-evoked firing frequency, or postsynaptic responses to exogenously applied glutamate. 4. The effects of (-)-baclofen on the DPSPs were compared to those produced by application of GABA and muscimol. GABA and muscimol decreased the DPSPs and caused a membrane depolarization coupled with a decrease of the membrane resistance. Bicuculline (100 microM) blocked the GABA-induced changes of the membrane potential and of the resistance, but not the decrease of the synaptic potentials. All the effects produced by muscimol were blocked by bicuculline. 5. Following intrastriatal stimulation a residual kynurenate-insensitive potential persisted; this potential was blocked by bicuculline (100 microM). (-)-Baclofen produced a dose-dependent decrease of this potential (EC50 = 800 nM). The postsynaptic responses to exogenously applied GABA were unchanged by (-)-baclofen. 6. The amplitude of kynurenate and bicuculline-sensitive DPSPs were stable at a frequency of 0.1 Hz. At frequencies between 0.3 and 3 Hz both these potentials were attenuated with the second stimulus and after about five stimuli a steady state was reached. Membrane potential and input resistance were not affected by these frequencies of stimulation. 7. Application of the GABA uptake inhibitor nipecotic acid (100-300 microM) clearly reduced the amplitude of both kynurenate-and bicuculline-sensitive DPSPs evoked at low frequencies of stimulation (0.01-0.3 Hz), but had lower effects at higher stimulation rates (1-3 Hz). Application of nipecotic acid increased the duration of membrane responses to exogenously applied GABA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Endogenous GABA mediates presynaptic inhibition of spontaneous and evoked excitatory synaptic potentials in the rat neostriatum.

The effect of the blockade of the gamma-aminobutyric acid (GABA) uptake system on the amplitude of glutamatergic synaptic potentials was studied by using a corticostriatal slice preparation. Nipecotic acid (0.1-1 mM), a GABA uptake blocker, produced a dose-dependent decrease of the amplitude of kynurenate-sensitive excitatory synaptic potentials recorded in the neostriatum following cortical stimulation. Nipecotic acid did not affect the postsynaptic responses to exogenously applied glutamate. The presynaptic effect of endogenous GABA was bicuculline-resistant and was mimicked by baclofen (0.3-3 microM). This effect was not blocked by phaclofen (0.5-1 mM). These findings show that phaclofen-insensitive GABAB receptors, activated by endogenous GABA, mediate presynaptic inhibition of cortical glutamatergic inputs in the neostriatum.

Animals↗
PubMed1990

Reliability of prenatal diagnosis of genetic diseases by analysis of amplified trophoblast DNA.

Dot blot analysis on enzymatically amplified trophoblast DNA with allele specific oligonucleotide probes is currently used for the prenatal diagnosis of single gene disorders characterised at the molecular level, such as the beta thalassaemias, phenylketonuria, sickle cell anaemia, and alpha 1-anti-trypsin deficiency. A potential problem with the use of this procedure is the co-amplification of maternal sequences, which may obscure the diagnosis in the fetus. To address this question, we carried out prenatal diagnosis of beta thalassaemia in 300 couples at risk by dot blot analysis on enzymatically amplified DNA with 32P or horseradish peroxidase labelled allele specific oligonucleotide probes. We verified the diagnosis obtained by this procedure with oligonucleotide hybridisation on electrophoretically separated non-amplified trophoblast DNA fragments. We detected no co-amplified maternal sequences, even with a faint signal, in the dot blot of trophoblast DNA from those fetuses diagnosed as normal or homozygotes, nor in those diagnosed as heterozygotes, who were born to parents carrying different mutations and had inherited the paternal mutation. These results indicate that, when careful dissection of trophoblast tissue from maternal decidua is carried out, amplification of chorionic villi DNA is not associated with amplification of maternal DNA sequences. We may thus conclude that dot blot analysis of trophoblast DNA is a very reliable procedure for prenatal diagnosis.

Chorionic Villi Sampling↗
PubMed1990

Kainic acid on neostriatal neurons intracellularly recorded in vitro: electrophysiological evidence for differential neuronal sensitivity.

The electrophysiological effects produced by different concentrations of kainic acid (KA) were studied by utilizing intracellular recordings from neostriatal slices. In most of the recorded cells (81%), concentrations of KA ranging between 10 and 300 nM produced reversible and dose-dependent membrane depolarizations. Higher concentrations of this agonist caused larger depolarizations and changes of the membrane properties of the recorded neurons not reversible during the time of recording. In a smaller percentage (19%) of the recorded cells, 10-100 nM KA did not produce significant membrane depolarizations; in these neurons, the depolarizations produced by higher concentrations of KA were small and reversible. The 2 populations of neurons showed similar electrophysiological properties and did not reveal differential sensitivity to quisqualic acid (QUIS; 10-30 microM) or to NMDA (10-30 microM). Tetrodotoxin (TTX; 1 microM) did not reduce the depolarizations produced by KA and by NMDA. Low-calcium, cobalt-containing solutions abolished the effects produced by NMDA, but not the KA-induced depolarizations. Kynurenic acid (500 microM) significantly antagonized the depolarizations produced by KA and reduced the changes of the membrane properties caused by high doses of this agonist. In several neurons, KA induced bicuculline-sensitive synaptic depolarizing potentials. Our findings suggest the presence of 2 subpopulations of neostriatal neurons showing differential postsynaptic sensitivity to KA. The differential sensitivity of neostriatal neurons to KA might influence the responses of these cells to glutamatergic cortical inputs and the degenerative changes observed in neostriatal neurons in some pathological conditions.

Action Potentials↗
PubMed1980

Decrease in human plasma prolactin levels by oral prostaglandin E2 in early puerperium.

Eight milligrams of prostaglandin E2 (PGE2; 2 mg every 30 min) were given orally to 12 puerperal women on day 4 after delivery. Plasma levels of prolactin showed a significant decrease in comparison with basal levels and with those of controls sampled over a similar period. The same dose of PGE2 was ineffective in modifying the plasma prolactin levels in four puerperal women on day 30 after delivery and in four non-pregnant women with normal levels of prolactin. It is suggested that a PGE2-induced decrease in prolactin could be mediated by hypothalamic dopaminergic neurones.

Female↗
PubMed1977

Inhibitory effect of prostaglandin F2alpha (PgF2alpha) on puerperal lactation.

Twenty puerperal women in 4th day after delivery were treated with a saline infusion containing 10 mg of PgF2alpha. Milk secretion, breast engorgement, prolactin plasma levels and side effects were determined. In all patients lactation disappeared within 48 hours after PgF2alpha infusion. During the following 12 hours after PgF2alpha treatment the prolactin plasma levels showed an important and significant decrease in all cases. In the following days the prolactin plasma levels decreased such as in normal puerperium. In some cases low gastralgia and in one case diarrhoea compaired. These results can be explained by PgF2alpha double action either on pituitary-hypothalamic function or on mammary gland cells.

Adult↗