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J Glowinski

Publications and source records attributed to J Glowinski.

At least 199 records · Page 11Linked to original sources
PubMed1990

Marked regional heterogeneity of 125I-Bolton Hunter substance P binding and substance P-induced activation of phospholipase C in astrocyte cultures from the embryonic or newborn rat.

The specific binding of 125I-Bolton Hunter substance P (125I-BHSP) was estimated on 4- to 5-week-old primary cultures of astrocytes from several brain structures and the spinal cord of 16-day-old embryonic or newborn rats. In both cases, high levels of binding of 125I-BHSP were found on intact astrocytes from the brainstem, but this binding was low or negligible on cells from the cerebral cortex, striatum, hypothalamus, and mesencephalon. In addition, hippocampal astrocytes from newborn rats were also devoid of 125I-BHSP binding sites, while a binding of 125I-BHSP (half that of brainstem cells) was observed on astrocytes from the cerebellum and spinal cord. It was also shown that this regional heterogeneity in 125I-BHSP binding was not linked to differences in the inactivation of the ligand, cell plating density. or eventual cell contaminants. Five-day-old cultures from 16-day-old embryos were used to estimate 125I-BHSP binding on neuron-enriched cultures. Specific 125I-BHSP binding was found on cells from the brainstem, mesencephalon, and hypothalamus, but neurons from the cerebral cortex or the striatum contained low or negligible amounts of 125I-BHSP binding sites. Competition studies using tachykinins and SP analogues indicated that 125I-BHSP binding sites on brainstem astrocytes (16-day-old embryos) have the pharmacological profile expected for NK1 binding sites. SP (1 microM) stimulated phosphoinositide breakdown in cells rich in 125I-BHSP binding sites (brainstem) but not in those devoid of 125I-BHSP binding (striatum).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pretreatment of mouse striatal neurons in primary culture with 17 beta-estradiol enhances the pertussis toxin-catalyzed ADP-ribosylation of G alpha o,i protein subunits.

Pretreatment of striatal neurons from mouse embryos in primary culture with 17 beta-estradiol (10(-9) M, 24 h) enhanced the ADP-ribosylation of G alpha o,i proteins catalyzed by pertussis toxin (PTX). As estimated by quantitative ADP-ribosylation of G alpha s with cholera toxin and immunoblot experiments using anti-G alpha o and anti-G beta sera, 17 beta-estradiol pretreatment did not modify the levels of the major GTP-binding protein (G protein) constituent subunits G alpha s, G alpha o, and G beta. Thus, 17 beta-estradiol should induce a qualitative modification of these G proteins, perhaps by stabilizing the association of the heterotrimers G alpha o,i beta gamma, which are the targets of PTX. Such a hypothesis is in agreement with observations indicating that 17 beta-estradiol both suppressed the D2 dopamine- and opiate receptor-induced inhibitions of adenylate cyclase activity and enhanced the positive coupling between biogenic amine receptors (D1 dopamine, beta-adrenergic, and A2 adenosine) and adenylate cyclase. In addition, PTX pretreatment, which is known to uncouple receptors associated with Go,i proteins and thus to impair the dissociation of the heterotrimers G alpha o,i beta gamma, mimicks the effects of the steroid on the responses of adenylate cyclase to inhibitory and stimulatory agonists. Finally, the chemical specificity of the steroids was the same in the ADP-ribosylation as in the adenylate cyclase experiments: Testosterone (10(-9) M) mimicked the effects of 17 beta-estradiol, whereas 17 alpha-estradiol, progesterone, and dexamethasone did not.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Chloroadenosine↗
PubMed1990

Involvement of dopamine neurons in the regulation of beta-adrenergic receptor sensitivity in rat prefrontal cortex.

The contribution of dopamine (DA) afferents to the regulation of beta-adrenergic receptor sensitivity (isoproterenol-stimulated adenylate cyclase activity) in the rat prefrontal cortex was investigated by comparing the effects of lesions affecting either both DA and noradrenaline (NA) or NA fibers alone. Bilateral 6-hydroxydopamine (6-OHDA) lesions made in the ventral tegmental area destroyed ascending DA and to a variable extent ascending NA fibers innervating the prefrontal cortex. Two opposite effects were observed depending on the extent of cortical NA denervation: (a) When NA denervation was complete (less than 4% of controls), a marked increase in the isoproterenol-sensitive adenylate cyclase activity (+78%) was found. The amplitude of this denervation supersensitivity was similar to that occurring following complete and selective destruction of NA innervation induced by bilateral 6-OHDA injections made into the pedunculus cerebellaris superior. (b) When 6-OHDA injections into the ventral tegmental area led to a partial destruction of cortical NA afferents (10-40% of control values), a hyposensitivity of the isoproterenol-induced adenylate cyclase activity (-30%) was observed. This effect contrasted with the moderate supersensitivity seen in rats with partial, but selective, destruction of NA innervation (pedunculus cerebellaris superior lesions). The hyposensitivity of beta-adrenergic receptors obtained in rats with partial lesions of cortical NA fibers, but devoid of cortical DA innervation, suggests that DA neurons may regulate, under certain conditions, the denervation supersensitivity of beta-adrenergic receptors.

Adenylyl Cyclases↗
PubMed1990

Competitive inhibition of N-acetylated-alpha-linked acidic dipeptidase activity by N-acetyl-L-aspartyl-beta-linked L-glutamate.

The endogenous neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) fulfills several criteria required to be accepted as a neurotransmitter. NAAG inactivation may proceed through enzymatic hydrolysis into N-acetyl-L-aspartate and glutamate by an N-acetylated-alpha-linked acidic dipeptidase (NAALADase). Therefore, some properties of NAALADase activity were investigated using crude membranes from the rat forebrain. Kinetic parameters of the hydrolysis of [Glu-3H]NAAG were determined first (Km = 0.40 +/- 0.05 microM; Vmax = 155 +/- 20 pmol/min/mg of protein). The enzymatic activity, i.e., NAALADase, was inhibited noncompetitively by the glutamatergic agonist quisqualate (Ki = 1.9 +/- 0.3 microM), and competitively by N-acetyl-L-aspartyl-beta-linked L-glutamate (beta-NAAG; Ki = 0.70 +/- 0.05 microM). To determine whether glutamate-containing dipeptides, such as NAAG, beta-NAAG, N-acetyl-L-aspartyl-D-glutamate, L-aspartyl-L-glutamate, L-alanyl-L-glutamate, L-glutamyl-L-glutamate, and L-glutamyl-gamma-linked L-glutamate, were substrates of NAALADase, rat brain membranes were immobilized on a C-8 column. Thus, endogenous trapped glutamate was washed away and formation of unlabelled glutamate could be estimated using an o-phthaldialdehyde/reverse-phase HPLC detection procedure. beta-NAAG was shown to be a nonhydrolyzable competitive inhibitor of NAALADase. L-Aspartyl-L-glutamate was hydrolyzed faster than NAAG, suggesting that the acetylated moiety is not essential for NAALADase specificity. Rat brain membranes also contained nonspecific peptidase activities (insensitive to both quisqualate and beta-NAAG), which, in the case of L-alanyl-L-glutamate, for instance, accounted for all observed hydrolysis.

Animals↗
PubMed1990

Selective agonists of tachykinin binding sites.

Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.

Amino Acid Sequence↗
PubMed1989

Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat.

Afferent connections of the medial and lateral prefrontal cortex of the rat arising from the hippocampal formation were investigated using iontophoretic application of the fluorescent tracer, Fluoro-gold. Our results demonstrate that the projection which originates in the temporal part of the CA1 hippocampal field and in the prosubiculum is restricted to the prelimbic area of the prefrontal cortex.

Animals↗
PubMed1989

Glycine potentiates the NMDA-induced release of dopamine through a strychnine-insensitive site in the rat striatum.

A new procedure, involving a push-pull cannula, was used to estimate the release of [3H]dopamine ([3H]DA) synthesized from [3H]tyrosine in rat striatal slices. NMDA (5 x 10(-5) M) stimulated [3H]DA release in the absence of Mg2+, and this effect was abolished in the presence of Mg2+ (10(-3) M), MK-801 (10(-6) M) or kynurenate (10(-4) M). Glycine markedly potentiated the NMDA-evoked response and reversed the inhibitory effect of kynurenate in the absence of Mg2+ and in the presence of strychnine (10(-6) M).

Animals↗
PubMed1989

Effect of noxious tail pinch on the discharge rate of mesocortical and mesolimbic dopamine neurons: selective activation of the mesocortical system.

The effects of noxious tail pinch on the activity of mesocortical and mesolimbic dopamine (DA) neurons located in the ventromedial mesencephalic tegmentum were analyzed in ketamine-anesthetized rats. The great majority of mesocortical DA neurons responded to tail pinch, either by an excitation (65%), or by an inhibition (25%). In contrast, most DA neurons projecting either to the nucleus accumbens or the septum remained unaffected. These results demonstrate that noxious tail pinch selectively influences the firing rate of mesocortical DA neurons.

Action Potentials↗
PubMed1989

Three-dimensional organization of the striosomal compartment and patchy distribution of striatonigral projections in the matrix of the cat caudate nucleus.

Acetylcholinesterase staining on successive frontal or sagittal sections was used to determine the three-dimensional organization of the striosomal and matrix compartments in the adult cat caudate nucleus. Reconstruction drawings of the acetylcholinesterase-poor zones (striosomes) indicated that the striosomal compartment is a labyrinthine network organized in the rostrocaudal and mediolateral axis which is reproducible from one animal to another. Four main anteroposterior channels converging in the mediorostral pole of the caudate nucleus were distinguished. Seven to eight diagonally oriented channels crossing the previous ones were seen also in the mediolateral axis on the central core of the caudate nucleus. The pattern of organization of the numerous and tortuous striosomal channels was more complicated medially, while the lateral part of the caudate nucleus was represented mainly by the matrix compartment. In addition, a sub-compartmentation of the matrix was demonstrated by retrograde tracing studies made by injecting either horseradish peroxidase-wheat germ agglutinin, [14C]amino acids or a mixture of horseradish peroxidase-wheat germ agglutinin and [14C]amino acids in several areas of the substantia nigra pars reticulata. Labelled patches were seen with both tracers, their topographical localization depended on the nigral injection site but reconstruction analysis indicated that the populations of cells which innervate the substantia nigra pars reticulata originate in the two third lateral parts of the caudate nucleus all along its rostrocaudal extension. Examination of horseradish peroxidase-wheat germ agglutinin labelled cells indicated that not all cells were labelled in patches suggesting a further sub-compartmentation of these patches. Finally, a comparison of the topographical distributions of labelled patches and of striosomes revealed that most patches were located in the extrastriosomal matrix.

Acetylcholinesterase↗
PubMed1989

Activation of the bilateral corticostriatal glutamatergic projection by infusion of GABA into thalamic motor nuclei in the cat: an in vivo release study.

The unilateral application of GABA (10(-5) M; 30 min) into thalamic motor nuclei of the cat increases the release of dopamine in both caudate nuclei. This effect has been suggested to be related to an activation of the bilateral corticostriatal glutamatergic projection, glutamate exerting a presynaptic facilitatory influence on dopamine release. To explore this hypothesis further, halothane-anesthetized cats implanted with push-pull cannulae were used in order to examine the effects of such a GABA application on the release of glutamate in both caudate nuclei. Aspartate, alanine, glutamine, serine and tyrosine were also measured in the superfusates. The unilateral application of GABA (10(-5) M; 30 min) into thalamic motor nuclei increased the release of glutamate bilaterally. Although less pronounced, ipsi- or bilateral increases in the efflux of alanine, glutamine and tyrosine were also observed. Contralateral changes in the efflux of glutamate, alanine and tyrosine were prevented following acute section of the corpus callosum. In addition, when applied continuously into one caudate nucleus, 2-amino-5-phosphonovaleric acid, a blocker of N-methyl-D-aspartate receptors, prevented the GABA-induced increase in alanine or tyrosine efflux but did not affect the enhanced release of glutamate. These results confirm that the unilateral application of GABA in thalamic motor nuclei activates a thalamo-cortico-striatal neuronal loop leading to the stimulation of glutamate release in both caudate nuclei. Changes in the efflux of other amino acids could be linked to increased metabolic activity of striatal target cells resulting from the increased release of glutamate and from its effect on N-methyl-D-aspartate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1989

Cyclic AMP reduces adhesion of isolated neuronal growth cones from developing rat forebrain to an astrocytic cell line from embryonic mouse striatum.

We have recently shown that isolated neuronal growth cones from developing rat forebrain possess an appreciable activity of adenylate cyclase, producing cyclic adenosine monophosphate, which can be stimulated by various neurotransmitter receptor agonists and by forskolin [Lockerbie R. O., Hervé D., Blanc G., Tassin J. P. and Glowinski J. (1988) Devl Brain Res. 38, 19-25]. In the present study, we have investigated the effect of cyclic adenosine monophosphate in an in vitro adhesion assay established between [3H]GABA-labelled isolated growth cones and a Simian virus-40 transformed astrocytic cell line from embryonic mouse striatum. Adhesion of the isolated growth cones onto the astrocytic clone increased steadily up to about 45 min before it began to level off at ca 16-18% of total [3H]GABA-labelled isolated growth cones added. Adhesion of the isolated growth cones onto the astrocytic clone was much superior to that seen on polyornithine and, in particular, on non-treated tissue culture wells. Adhesion "at plateau" was independent of both temperature and extracellular Ca2+ and was markedly reduced (ca 50%) by trypsin pre-treatment of the isolated growth cones. Pre-treatment of the isolated growth cones with either forskolin or lipophilic analogues of cyclic adenosine monophosphate attenuated adhesion in a time- and concentration-dependent manner. Approximately 30% reduction in adhesion to the astrocytic clone "at plateau" was observed after a 15 min pre-treatment of the isolated growth cones with forskolin at 10(-4) M or cyclic adenosine monophosphate analogues at 10(-3) M. A cyclic guanosine monophosphate analogue was without effect on adhesion of isolated growth cones. Scanning electron microscope analysis showed that isolated growth cones pre-treated with either cyclic adenosine monophosphate analogues or forskolin had a simpler morphology when attached to the astrocytic clone than isolated growth cones under control conditions. Pre-treatment of the isolated growth cones with low concentrations of cyclic adenosine monophosphate analogues increased protein kinase activity, measured using an exogenous histone phosphate acceptor, to a level which could not be further stimulated by cyclic adenosine monophosphate. Pre-treatment with a cyclic guanosine monophosphate analogue produced the same effect but only at much higher concentrations than those required for cyclic adenosine monophosphate analogues.

Animals↗
PubMed1989

Distinct presynaptic control of dopamine release in striosomal and matrix areas of the cat caudate nucleus.

By use of a sensitive in vitro microsuperfusion method, the cholinergic prsynaptic control of dopamine release was investigated in a prominent striosome (areas poor in acetylcholinesterase activity) located within the core of cat caudate nucleus and also in adjacent matrix area. The spontaneous release of [3H]dopamine continuously synthesized from [3H]tyrosine in the matrix area was found to be twice that in the striosomal area; the spontaneous and potassium-evoked releases of [3H]dopamine were calcium-dependent in both compartments. With 10(-6) M tetrodotoxin, 5 x 10(-5) M acetylcholine stimulated [3H]dopamine release in both striosomal and matrix areas, effects completely antagonized by atropine (10(-6) M), thus showing the involvement of muscarinic receptors located on dopaminergic nerve terminals. Experiments without tetrodotoxin revealed a more complex regulation of dopamine release in the matrix: (i) In contrast to results seen in the striosome, acetylcholine induced only a transient stimulatory effect on matrix dopamine release. (ii) Although 10(-6) M atropine completely abolished the cholinergic stimulatory effect on [3H]dopamine release in striosomal area, delayed and prolonged stimulation of [3H]dopamine release was seen with atropine in the matrix. The latter effect was completely abolished by the nicotinic antagonist pempidine (10(-5) M). Therefore, in the matrix, in addition to its direct (tetrodotoxin-insensitive) facilitatory action on [3H]dopamine release, acetylcholine exerts two indirect (tetrodotoxin-sensitive) opposing effects: an inhibition and a stimulation of [3H]dopamine release mediated by muscarinic and nicotinic receptors, respectively.

Acetylcholine↗
PubMed1989

Pharmacological and functional heterogeneity of astrocytes: regional differences in phospholipase C stimulation by neuromediators.

Carbamylcholine stimulated phospholipase C activity in astrocytes in primary culture from the mesencephalon but not from the striatum or cerebral cortex of the mouse embryo. An alpha 1-adrenergic-mediated response was observed in all astrocyte populations. 2-Chloroadenosine potentiated the alpha 1-adrenergic response in mesencephalic and striatal astrocytes but not in cortical astrocytes. It also stimulated the carbamylcholine-evoked response in mesencephalic astrocytes. Through cell-cell cooperation, 2-chloroadenosine potentiated the neuronal carbamylcholine-evoked activation of phospholipase C in homotopic cocultures (neuro-glial) from the striatum but not in homotopic cocultures (neuro-glial) from the cerebral cortex or in heterotopic cocultures (cortical astrocytes-striatal neurons; striatal astrocytes-cortical neurons.

2-Chloroadenosine↗
PubMed1989

Tachykinin receptors of the NK1 type (substance P) coupled positively to phospholipase C on cortical astrocytes from the newborn mouse in primary culture.

Specific 125I-Bolton-Hunter substance P (125I-BHSP) binding sites are present on intact cortical astrocytes of the newborn mouse in primary culture. Therefore, these cells were used to ascertain the existence of functional substance P (SP) receptors coupled positively to phospholipase C. SP stimulated phosphoinositide breakdown with an EC50 value (4.5 x 10(-10) M) similar to its IC50 value (3.8 x 10(-10) M) for inhibiting 125I-BHSP binding. The maximal response to (10(-6) M SP for 60 min) obtained was approximately 500% of control values. The rank order of potency of tachykinins was SP greater than neurokinin (NK) A greater than NKB. Long SP C-terminal fragments were more potent than shorter ones in stimulating the accumulation of 3H-inositol phosphates. SP free acid and SP N-terminal fragments were without effect. [L-Pro9]SP and SP methyl ester, two selective agonists of NK1 receptors, were almost as potent as SP. An excellent correlation was found when the abilities of tachykinins and their analogs for stimulating phosphoinositide breakdown and for inhibiting 125I-BHSP binding were compared. Finally, when used at a concentration of 3 x 10(-6) M, spantide [( D-Arg1, D-Trp7,9, Leu11]SP), an SP antagonist, competitively reduced the stimulatory effect of SP on accumulation of 3H-inositol phosphates. These results demonstrate the presence of functional SP receptors (NK1) on cortical astrocytes from the newborn mouse in primary culture.

Animals↗
PubMed1989

Substance P-induced reduction in the initial accumulation of cytosolic myo-[3H]inositol in rat parotid acinar cells mediated by the NK1 tachykinin receptor.

Stimulation of rat parotid acinar cells by the tachykinin neurokinin (NK) 1 receptor agonist substance P (SP) resulted in a significant reduction in the initial accumulation of cytosolic myo-[3H]inositol. This effect was rapid, because a reduction of approximately 15% could be seen already at 30 s. with the maximal effect (approximately 45%) being observed at 15 min. The response to SP stimulation was temperature dependent, because at 4 degrees C no reduction was found. In addition, at 4 degrees C, cytosolic myo-[3H]inositol represented only 10% of the labeled inositol accumulated at 37 degrees C. The SP-induced reduction in cytosolic myo-[3H]inositol accumulation was concentration dependent; the EC50 obtained for SP was 5.8 +/- 2.5 nM. Spantide [D-Arg1, D-Trp7.9, Leu11]SP), a SP antagonist, used at a concentration of 10(-5) M, gave a competitive shift of the dose-response curve to SP. Various tachykinins and their analogs were evaluated for their ability to reduce cytosolic myo-[3H]inositol. [L-Pro9]SP and SP methyl ester, two highly selective agonists of NK1 receptors, reduced the initial accumulation of myo-[3H]inositol with EC50 values of 2.3 and 67.0 nM, respectively. Long SP C-terminal fragments were more potent than shorter ones. SP N-terminal fragments and SP free acid were without effect. [Pro7]NKB, a selective NKB analog, had no effect. The rank order of potency of mammalian tachykinins was SP greater than NKA greater than NKB. These findings and the close correlation between EC50 values and IC50 values obtained in binding studies implicate the NK1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Differential modulation of D1 and D2 dopamine-sensitive adenylate cyclases by 17 beta-estradiol in cultured striatal neurons and anterior pituitary cells.

Primary cultures of anterior pituitary cells from female rats and of mouse embryonic striatal neurons were used to study the effects of 17 beta-estradiol on D1- and D2-dopamine (DA)-sensitive adenylate cyclase. 17 beta-Estradiol pretreatment (10(-9) M, 72 h) suppressed the D2-DA-induced inhibition of adenylate cyclase activity in anterior pituitary cells. The steroid (10(-9) M, 24 h) also blocked the D2-DA-evoked response in striatal neurons whereas it enhanced by twofold the D1-DA-induced stimulation of the enzyme activity in these neurons. All these effects of the steroid were dose dependent and specific, as neither 17 alpha-estradiol, dexamethasone, nor progesterone used at the same concentration (10(-9) M) was effective. Furthermore, the modulation of DA-sensitive adenylate cyclases by the steroid required long-term exposure of living cells to 17 beta-estradiol since neither 17 beta-estradiol pretreatment for 4 h nor its addition to broken cells directly into the adenylate cyclase assay induced any alteration in the DA-sensitive adenylate cyclase activity. These results are in agreement with a genomic effect of the steroid. Using both anterior pituitary cells and striatal neurons in culture, 17 beta-estradiol affected neither the total number of DA (D1 and D2) receptors nor the estimated number of adenylate cyclase catalytic units. Therefore, it is suggested that the steroid modifies the coupling process by a mechanism that still has to be elucidated. These results demonstrate an effect of 17 beta-estradiol on DA target cells in both systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1989

Stathmin is a major phosphoprotein and cyclic AMP-dependent protein kinase substrate in mouse brain neurons but not in astrocytes in culture: regulation during ontogenesis.

Stathmin is a ubiquitous soluble protein (Mr approximately 19,000; pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. It is present in various tissues and cell types and has several nonphosphorylated and increasingly phosphorylated forms, and it is particularly abundant in brain. Very high concentrations of stathmin were also detected in mouse embryo striatal neurons grown in primary culture, whereas stathmin was barely detectable in astrocytes from the same source. Stathmin appeared in neurons as a major substrate for protein phosphorylation and, in particular, for the cyclic AMP (cAMP)-dependent protein kinase, because its phosphorylation was stimulated by cAMP in cell-free preparations and in intact cells by forskolin, a potent activator of adenylate cyclase. During brain ontogenesis, stathmin was first detected at embryonic day 12; its concentration increased until birth and then decreased from postnatal day 10 to adulthood. In parallel, its molecular forms shifted from the least phosphorylated to the more phosphorylated ones. This result may reflect the evolution of the activity of stathmin during development and the subsequent maturation of the brain. In conclusion, our results substantiate the likely role of stathmin as an intracellular relay of extracellular regulations, as they point out its specific importance related to neuronal functions and brain differentiation.

1-Methyl-3-isobutylxanthine↗