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P Marin

Publications and source records attributed to P Marin.

18 recordsLinked to original sources
PubMed1992

Nitric oxide-induced blockade of NMDA receptors.

We studied the effects of nitric oxide (NO)-producing agents on N-methyl-D-aspartate (NMDA) receptor activation in cultured neurons. 3-Morpholino-sydnonimine (SIN-1) blocked both NMDA-induced currents and the associated increase in intracellular Ca2+. The actions of SIN-1 were reversible and suppressed by hemoglobin. A degraded SIN-1 solution that did not release NO was unable to block NMDA receptors. This showed that the SIN-1 effects were due to NO and not to another breakdown product. Similar results were obtained with 1-nitrosopyrrolidine (an NO-containing drug) and with NO released from NaNO2. Pretreatment with hemoglobin potentiated NMDA-induced effects, demonstrating that endogenous NO modulates NMDA receptors. Since NMDA receptor activation induces NO synthesis, these results suggest a feedback inhibition of NMDA receptors by NO under physiological condition.

Animals↗
PubMed1992

Synergistic regulation of cytosolic Ca2+ concentration by somatostatin and alpha 1-adrenergic agonists in mouse astrocytes.

The effects of somatostatin and alpha 1-adrenergic receptor agonists on cytosolic Ca2+ in striatal astrocytes from the embryonic mouse in primary culture have been investigated by microfluorimetry. Methoxamine or somatostatin induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+ which seems to be due to a Ca2+ influx since it was not observed in the absence of external Ca2+. Voltage-independent Ca2+ channels contribute to this process. Indeed, voltage-operated calcium channels are not involved since neither dihydropyridines nor La3+ were effective in suppressing the sustained cytosolic Ca2+ elevation. Moreover, depolarization by 50 mM KCl, which was ineffective alone, suppressed the effect of somatostatin observed in the presence of the alpha 1 agonist, methoxamine. The implication of arachidonic acid in the observed potentiation is suggested by the following observations: 1) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the co-application of methoxamine and somatostatin; 2) the addition of ETYA, an inactive and non-metabolizable analogue of arachidonic acid suppressed the calcium plateau produced by the agonists. In addition, direct activation of PKC by an exogeneous diacylglycerol analogue allowed somatostatin alone to evoke a sustained elevation of cytosolic Ca2+. Therefore, methoxamine through the successive activation of PLC and PKC could allow a lipase, probably PLA2, to be stimulated by somatostatin. Since arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates, somatostatin, through the arachidonic acid-mediated hyperpolarization could increase the Ca2+ driving force and thus improve Ca2+ influx through the inositol phosphate gated channels.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1992

2-Chloroadenosine potentiates the alpha 1-adrenergic activation of phospholipase C through a mechanism involving arachidonic acid and glutamate in striatal astrocytes.

In cultured striatal astrocytes, 2-chloroadenosine, an adenosine analog resistant to adenosine deaminase, although inactive alone, markedly potentiated the activation of phospholipase C induced by methoxamine, an alpha 1-adrenergic agonist. This effect was suppressed by antagonists of either A1 adenosine or alpha 1-adrenergic receptors. An influx of calcium and two distinct G-proteins are involved in this phenomenon since the potentiating effect of 2-chloradenosine was suppressed in the absence of external calcium or when cells were pretreated with pertussis toxin. In addition, arachidonic acid is likely involved in this potentiating effect. This was shown first by examining the effects of inhibitors of phospholipase A2 or arachidonic metabolism, then by examining the action of arachidonic acid on the production of inositol phosphates in either the presence or absence of methoxamine, and finally by measuring the release of arachidonic acid. The sequential activation of phospholipase C and of protein kinase C is required for the 2-chloroadenosine-induced activation of phospholipase A2 since 2-chloroadenosine markedly stimulated phospholipase C activity in the absence of methoxamine when protein kinase C was activated by a diacylglycerol analog. Finally, the enhancing effect of 2-chloroadenosine on the methoxamine-evoked response seems to result from an inhibition of glutamate reuptake into astrocytes by arachidonic acid. Indeed, the potentiating effect of 2-chloroadenosine was suppressed when external glutamate was removed enzymatically and mimicked by either selective inhibitors of the glutamate reuptake process or direct application of glutamate.

2-Chloroadenosine↗
PubMed1991

Somatostatin potentiates the alpha 1-adrenergic activation of phospholipase C in striatal astrocytes through a mechanism involving arachidonic acid and glutamate.

As previously shown with adenosine, somatostatin, which is ineffective alone, enhanced the alpha 1-adrenergic-agonist-stimulated production of inositol phosphates in cultured striatal astrocytes. This effect was suppressed in cells pretreated with pertussis toxin. It required external calcium and was selectively antagonized by both mepacrine, an inhibitor of phospholipase A2, and 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable analog of arachidonic acid. In addition, a long-lasting elevation of cytosolic calcium and a release of arachidonic acid were observed only under the combined stimulation of somatostatin and alpha 1-adrenergic receptors. Arachidonic acid could in turn inhibit glutamate uptake into astrocytes, and the resulting external accumulation of glutamate could account for the somatostatin-evoked amplification of the alpha 1-adrenergic-agonist-stimulated hydrolysis of inositol-phospholipids. The effect of somatostatin was indeed reproduced by glutamate or glutamate uptake inhibitors and suppressed by enzymatic removal of external glutamate. Thus, astrocytes may contribute to long-term plasticity events in glutamatergic synapses through regulation of external glutamate levels.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1991

Adrenergic regulation of intercellular communications between cultured striatal astrocytes from the mouse.

The permeability of gap junctions in cultured striatal astrocytes was investigated by the scrape-loading/dyetransfer technique. Prolonged application of norepinephrine (NE) (10 microM) reduced by half the extent of dye (Lucifer yellow) spread. This effect was linked to the activation of alpha 1-adrenergic receptors since it was mimicked by methoxamine and antagonized by prazosin. The adenosine agonist 2-chloroadenosine (10 microM), which potentiates the NE-evoked activation of phospholipase C (PLC) in striatal astrocytes, also potentiated the NE-evoked closure of gap junctions, the effect being as important as that observed with the uncoupling agent octanol. Measurements of inositol phospholipid turnover performed in identical experimental conditions revealed a close relationship between the extent of PLC activation and the magnitude of the uncoupling process. The effect of NE was mimicked by both phorbol ester and arachidonic acid, suggesting that biochemical events linked to PLC stimulation such as protein kinase C activation and/or eicosanoid production are likely involved in the NE-induced uncoupling. In addition, in the presence of a cAMP phosphodiesterase inhibitor, the stimulation of beta-adrenergic receptors by isoproterenol (10 microM) led to a large increase in cAMP accumulation correlated with an extension of dye diffusion. This observation suggests that junctional permeability could also be controlled by a cAMP-dependent mechanism. Altogether these results indicate that intercellular communication between cultured astrocytes can be regulated by different second messenger pathways as a result of the action of neurotransmitters on their receptors.

Animals↗
PubMed1991

Functional endothelin-1 receptors in rat astrocytoma C6.

Rat astrocytoma C6 cells have been recently identified as target cells for ET-1, which stimulates inositol lipid turnover in these cells. It is shown here that binding of ET-1 to high-affinity receptors on C6 cells leads to 40-45% inhibition of isoproterenol-induced intracellular cyclic AMP accumulation, as well as to stimulation of inositol lipid turnover, both effects characterized by an absolute requirement of extracellular calcium. Moreover, ET-1, which has been generally reported to have a mitogenic effect on a variety of target cells including primary rat astrocytes, is shown here to stimulate or, alternatively, inhibit DNA synthesis in C6 cells, depending on the subclone considered.

Animals↗
PubMed1991

Synergistic effects in the alpha 1- and beta 1-adrenergic regulations of intracellular calcium levels in striatal astrocytes.

1. Using indo-1 as a calcium fluorescent probe, we have observed the following in striatal astrocytes in primary culture. 2. The stimulation of alpha-adrenoceptors induces a rapid rise in cytosolic calcium resulting from an internal calcium mobilization followed by an external calcium influx (4-min duration). 3. The stimulation of beta 1-adrenoceptors evokes only a slight internal calcium mobilization (90-sec duration). 4. The simultaneous stimulation of beta 1- and alpha 1-adrenoceptors induces a more prolonged calcium influx (10 min). The latter phenomenon could explain the calcium-dependent synergistic effects of alpha 1 and beta stimulation on cAMP production already described in the brain.

Albuterol↗
PubMed1991

Comparison of binding characteristics of endothelin receptors on subpopulations of astrocytes.

Astrocytes in primary culture originating from different brain areas of the mouse embryo (striatum, cerebral cortex and mesencephalon) were compared for their [125I]-Endothelin-1 (ET-1) binding characteristics, in terms of affinity, binding capacity and specificity. Our results indicate that astrocytes from mesencephalon express about twice as many receptors as astrocytes from striatum or cortex (149,000 +/- 9700 vs 63,700 +/- 5600 and 81,900 +/- 5300, respectively), with similar affinities. Specificity patterns for the various peptides of the endothelins/sarafotoxins family (ET-1, -2, -3; SRTXa, b, c) are comparable in the three subpopulations of astrocytes: ET-1, -2 and SRTXb exhibit higher affinities than SRTXa and SRTXc. In addition, ET-3 and SRTXc seem to discriminate between different subsets of [125I]-ET-1 binding sites in the three subpopulations.

Animals↗
PubMed1991

Are several G proteins involved in the different effects of endothelin-1 in mouse striatal astrocytes?

High-affinity specific receptors of endothelin (ET-1) were identified on primary cultures of mouse embryo striatal astrocytes by binding experiments performed with 125I-ET-1. Stimulation of production of inositol phosphates, a biphasic increase of the intracellular calcium concentration, and inhibition of cyclic AMP accumulation were observed in the same cells under ET-1 stimulation. Pretreatment of these cells with Bordetella pertussis toxin affected these effects to different extends, an observation suggesting that they are mediated by multiple transduction pathways, possibly involving several guanine nucleotide-binding proteins.

Animals↗
PubMed1991

Hypernatraemia in an adult in-patient population.

We report a retrospective study of hypernatraemia (serum sodium concentration greater than 150 mmol/l) in an adult in-patient population of a health district during one year. The incidence was 0.3% with at least 60% of cases developing after hospital admission, mainly in elderly patients. Dehydration appeared to be the major cause, with the use of diuretics, depressed conscious level or febrile illness implicated in a majority. Most patients had more than one contributory factor and iatrogenic causes were common. Associated illnesses were often severe and the in-hospital mortality was high (54%) regardless of age. Hypernatraemia in hospitalized patients should be largely avoidable and there is a need for greater awareness of the importance of active maintenance of hydration in susceptible patients.

Adult↗
PubMed1990

Establishment of permanent astroglial cell lines, able to differentiate in vitro, from transgenic mice carrying the polyoma virus large T gene: an alternative approach to brain cell immortalization.

Permanent untransformed cell lines have been established from the cerebral cortex of transgenic mice that carry the polyoma virus large T gene. The immortalized cells described here synthesize laminin and neural cell adhesion molecules and induce primary neurons to develop neuritic processes. As shown by immunofluorescence and immunoblotting assays, they begin to synthesize the glial fibrillary acidic protein (GFAP) after confluence. Double labelling experiments indicated that GFAP expression is reversibly correlated with the arrest of cell division. The present cells also display adrenergic, serotoninergic, and high levels of muscarinic receptors coupled to the phosphatidylinositol signalling pathway. Taken together, our data show that these cell lines constitute homogeneous cell material that has retained the main differentiative, functional, and growth properties of normal astrocytes. Therefore, such clonal untransformed cell lines should be useful for further molecular studies, addressing terminal differentiation of glial cells, glioneuronal interactions, and astroglial expression of receptors for neurotransmitters. Furthermore, we suggest that this approach of cell immortalization by the use of transgenic mice carrying a non-transforming oncogene might be extended to a variety of cell types.

Animals↗
PubMed1990

Immortalization of bipotential and plastic glio-neuronal precursor cells.

Permanent clonal cell lines from newborn mouse striatum have been established after transfer of the simian virus 40 large tumor oncogene by means of a retroviral vector. Some of the lines obtained displayed properties of bipotential and plastic glio-neuronal precursors. Depending on the culture conditions, these cells express either the glial fibrillary acidic protein or neurofilaments. In addition, the cells can display adrenergic, D1 and D2 dopaminergic, muscarinic, and 5-hydroxytryptamine type 2 serotoninergic receptors, which are coupled either to the adenylate cyclase or to the phosphatidylinositol signaling pathways. The panel of receptors for neurotransmitters exhibited by these lines closely resembles that of primary striatal neurons. Results suggest that plastic common precursors of astrocytes and neurons persist in the striatum at a late developmental stage. As these permanent cell lines constitute an unlimited source of homogenous cell material, we suggest that they should be useful for molecular and pharmacological studies on the mechanisms and regulation of signal transduction as well as the commitment, plasticity, and differentiation of neural cells.

Animals↗
PubMed1990

Alternaria infection in a patient receiving chemotherapy for lymphoma.

A 60-year-old man receiving chemotherapy for an intermediate-grade non-Hodgkin's lymphoma developed multiple papuloerythematous cutaneous lesions. Alternaria alternata was cultured from the lesions, and hyphae were seen in biopsy specimens. This is an unusual infection, without a well-established treatment, in patients with lymphoma. The use of amphotericin B resulted in cure.

Alternaria↗