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J Glowinski

Publications and source records attributed to J Glowinski.

At least 181 records · Page 10Linked to original sources
PubMed1991

Role of dynorphin-containing neurons in the presynaptic inhibitory control of the acetylcholine-evoked release of dopamine in the striosomes and the matrix of the cat caudate nucleus.

The roles of acetylcholine and dynorphin (1-13) in the presynaptic control of the release of [3H]dopamine continuously synthesized from [3H]tyrosine were examined in a prominent striosomal enriched area and in an adjacent matrix enriched area of the cat caudate nucleus. This was achieved using microsuperfusion devices applied vertically onto coronal slices of cat brain. These devices were placed in a striosomal enriched area located in the core of the structure (acetylcholinesterase-poor zone) and in an adjacent matrix enriched area (acetylcholinesterase-rich zone). [3H]Tyrosine was delivered continuously to each microsuperfusion device and [3H]dopamine released was estimated in the superfusate. As previously shown, in the presence of tetrodotoxin (1 microM), acetylcholine (50 microM) induces a prolonged stimulation of [3H]dopamine release in both compartments through an interaction with muscarinic receptors. Our present study indicates that both dynorphin 1-13 (1 microM) and the selective kappa agonist trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl]benzeneace tamine (U50488) (1 microM) inhibit the tetrodotoxin-resistant acetylcholine-evoked release of [3H]dopamine, these effects being slightly more pronounced in the matrix than in the striosomal enriched area. Naloxone (1 microM) reversed the inhibitory effect of U50488 in both areas. These results suggest that dynorphin exerts an inhibitory presynaptic control of dopamine release through kappa opioid receptors located on dopamine nerve terminals in the striosome as well as in the matrix. However, the presynaptic cholinergic control of dopamine release is much more complex in the matrix than in the striosomal enriched area. Besides its tetrodotoxin-resistant stimulatory effect, acetylcholine exerts two opposing tetrodotoxin-sensitive effects on [3H]dopamine release, one facilitatory and the other inhibitory. We demonstrate here that in the superfused matrix enriched area, the indirect acetylcholine inhibitory response is mediated by dynorphin-containing neurons. Indeed, the short-lasting stimulatory effect of acetylcholine on [3H]dopamine release was converted into a long-lasting response in the presence of naloxone (1 microM), and, in this latter condition, the co-application of dynorphin 1-13 (1 microM) restored the short-lasting stimulatory effect.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Gap junctions in cultured astrocytes: single-channel currents and characterization of channel-forming protein.

Currents from gap junction channels were recorded from pairs of astrocytes in primary culture using the double whole-cell recording technique. In weakly coupled pairs, single-channel events could be resolved without pharmacological uncoupling treatment. Under these conditions, unitary conductance was 56 +/- 7 pS, and except for multiples of this value, no other level of conductance was observed consistently. To characterize the type of junctional protein constituting astrocyte gap junction channels, immunological and biochemical experiments were carried out on the same material. Specific cDNA probes for three connexins identified in mammals (Cx26, Cx32, and Cx43) showed that only Cx43 mRNA was expressed in cultured astrocytes. The presence of Cx43 protein in cultured astrocytes was demonstrated by immunoblotting, immunofluorescence, and immunogold labeling using anti-peptide antibodies specific to Cx43. These results strongly suggest that gap junctions in astrocytes have a 50-60 pS unitary conductance associated with channels composed of Cx43 protein.

Animals↗
PubMed1991

Further demonstration that [Pro9]-substance P is a potent and selective ligand of NK-1 tachykinin receptors.

Previous studies have indicated that [Pro9]-substance P ([Pro9]-SP) possesses very good affinity for NK-1 binding sites and that, in contrast to substance P, it interacts selectively with these sites. Therefore, [3H][Pro9]-SP (75 Ci/mmol) was synthesized in order to study its binding to membranes of the rat brain. Specific binding of [3H][Pro9]-SP (75% of total binding) was temperature-dependent, saturable, and reversible. Scatchard analysis and Hill plots revealed the existence of a single population of noninteracting binding sites (KD and Bmax values: 1.48 nM and 29.7 fmol/mg of protein, respectively). Competition studies with several tachykinins and analogues indicated that the pharmacological profile of [3H][Pro9]-SP binding sites is identical to that of NK-1 binding sites. Rat brain sections labeled with either [3H][Pro9]-SP or [3H]SP, revealed a close similarity in the topographical distribution of [3H][Pro9]-SP and [3H]SP binding sites. Biochemical, pharmacological, and autoradiographic data obtained with [3H][Pro9]-SP did not provide any evidence for the existence of subtypes of NK-1 binding sites. [Pro9]-SP had neither agonist nor antagonist properties on NK-2 and NK-3 receptors. Indeed, it did not stimulate phosphoinositide turnover on the hamster urinary bladder (NK-2 assay) and was devoid of activity on the contraction of the rabbit pulmonary artery (NK-2 assay) and of the rat portal vein (NK-3 assay). As a result of its high selectivity, [Pro9]-SP thus appears an excellent tool for investigating the functional properties of NK-1 receptors.

Animals↗
PubMed1991

Glutamatergic control of dopamine release in the rat striatum: evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals.

The N-methyl-D-aspartate (NMDA) receptor-mediated regulation of the release of newly synthesized [3H]dopamine [( 3H]DA) was studied in vitro, both on rat striatal slices using a new microsuperfusion device and on rat striatal synaptosomes. Under Mg2(+)-free medium conditions, the NMDA (5 X 10(-5) M)-evoked release of [3H]DA from slices was found to be partly insensitive to tetrodotoxin (TTX). This TTX-resistant stimulatory effect of NMDA was blocked by either Mg2+ (10(-3) M) or the noncompetitive antagonist MK-801 (10(-6) M). In addition, the TTX-resistant NMDA-evoked response could be potentiated by glycine (10(-6) M) in the presence of strychnine (10(-6) M). The coapplication of NMDA (5 X 10(-5) M) and glycine (10(-6) M) stimulated the release of [3H]DA from striatal synaptosomes. This effect was blocked by Mg2+ (10(-3) M) or MK-801 (10(-5) M). These results indicate that some of the NMDA receptors involved in the facilitation of DA release are located on DA nerve terminals. These presynaptic receptors exhibit pharmacological properties similar to those described in electrophysiological studies for postsynaptic NMDA receptors.

Animals↗
PubMed1991

Cyclic AMP accumulation induces a rapid desensitization of the cyclic AMP-dependent protein kinase in mouse striatal neurons.

Striatal neurons from the mouse brain embryo grown in primary culture express high levels of cyclic AMP (cAMP)-dependent protein kinase (PKA) activity. To study the modulation of PKA in intact neurons, a rapid method based on Zn(2+)-protein precipitation was developed. This strategy allowed analysis of the stimulation of PKA under conditions of intracellular cAMP concentration increases. Whereas increases up to 1 microM lead to an activation, large and sustained accumulations of cAMP result in a loss of the enzyme activity. With 8-bromo-cAMP (8-Br-cAMP) at 100 microM, the PKA refractoriness occurs within 2 min. It is rapidly reversible because incubation of treated neurons in fresh medium leads to a complete recovery of PKA activity within 30 min. The decrease in assayable PKA does not involve an activation of phosphatases because the histone dephosphorylation rate is not affected by 8-Br-cAMP treatment. Finally, not only 8-Br-cAMP- but also forskolin- and vasoactive intestinal peptide-induced increases in intracellular cAMP concentration can lead to the PKA desensitization. Altogether, these data unravel a new mechanism of PKA regulation.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Synergistic regulation of cytosolic Ca2+ concentration in mouse astrocytes by NK1 tachykinin and adenosine agonists.

The effects on cytosolic Ca2+ concentration of 2-chloroadenosine and [L-Pro9]-substance P, a selective agonist of NK1 receptors, were investigated on astrocytes from embryonic mice in primary culture. Cells responded to [L-Pro9]-substance P with a transitory increase in cytosolic Ca2+ which was of shorter duration when external Ca2+ was removed. A transient response to 2-chloroadenosine alone occurred. When simultaneously applied, [L-Pro9]-substance P and 2-chloroadenosine evoked a prolonged elevation of cytosolic Ca2+ (up to 30 min). This phenomenon was dependent on the presence of extracellular Ca2+, but insensitive to dihydropyridines, La3+, and Co2+, excluding the implication of voltage-operated Ca2+ channels. Arachidonic acid also induced a sustained elevation of cytosolic Ca2+, but did not increase further the response evoked by [L-Pro9]-substance P and 2-chloroadenosine. The activation of protein kinase C by a diacylglycerol analogue mimicked the effect of [L-Pro9]-substance P in potentiating the 2-chloroadenosine-evoked response. Like 2-chloroadenosine, pinacidil, which hyperpolarizes the cells by opening K+ channels, prolonged the elevation of cytosolic Ca2+ concentration induced by [L-Pro9]-substance P. Conversely, depolarization with 50 mM KCl canceled the effects of either pinacidil or 2-chloroadenosine applied with [L-Pro9]-substance P. Pertussis toxin pretreatment suppressed all the effects induced by 2-chloroadenosine.

2-Chloroadenosine↗
PubMed1991

Presynaptic facilitation of dopamine release through D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors on synaptosomes from the rat striatum.

Purified synaptosomes from the rat striatum were superfused continuously with [3H]tyrosine in order to estimate the release of newly synthesized [3H]dopamine. When tested from 10(-6) to 10(-3) M, several excitatory amino acids or their analogues markedly stimulated the release of [3H]dopamine, their apparent rank order of potency being kainate greater than glutamate = D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) greater than homocysteate greater than quisqualate greater than aspartate greater than ibotenate. N-acetyl-aspartyl-glutamate was without effect. In addition, in the range of concentrations of 10(-6) to 10(-3) M, the maximal response of glutamate was higher than that of kainate, AMPA or homocysteate, whereas the effects of quisqualate, aspartate and ibotenate, particularly, were of lower amplitude. In favor of the existence of glutamate receptors of the AMPA type on dopaminergic nerve terminals, the stimulatory effect of AMPA (5 x 10(-5) M) on [3H]dopamine release was antagonized by 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7-nitro-quinoxaline-2,3-dione, tau-D-glutamyl-amino-methyl-sulphonate and tau-D-glutamyl-glycine tested at 10(-4) M. 6,7-Dinitroquinoxaline-2,3-dione was the most potent, whereas L-glutamate diethylester was without effect. As expected D-2-amino-5-phosphonovalerate did not affect the AMPA-evoked response. Further experiments indicated that kainate and quisqualate stimulate the release of [3H]dopamine by acting on quisqualate/kainate or AMPA receptors. The quisqualate-evoked desensitization of AMPA receptors was prevented by concanavalin A (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inhibitory effects of substance P and carbachol on the saturable sodium-dependent uptake process of myo-inositol in rat parotid gland.

myo-Inositol uptake in prisms of rat parotid glands was investigated by measuring both the accumulation of free myo-[3H] inositol into the cytosol and its incorporation into phospholipids. Total myo-[3H]inositol uptake involved two distinct processes, a prominent one which is saturable and sodium-dependent (Km, 95 microM; Vmax, 8 pmol/mg of protein per min) and a minor one, nonsaturable and sodium-independent. Phloretin and cytochalasin B, two inhibitors of hexose transport, and D-glucose, but only at high concentrations (greater than 10 mM), inhibited myo-[3H]inositol uptake. Dixon plots of the data indicated that D-glucose inhibition was noncompetitive suggesting that myo-inositol and D-glucose are transported by different carriers. Electrogenic cotransport of sodium and myo-inositol, rather than energy derived from mitochondrial oxidative metabolism, seems to be involved in the transport process. Thus, ouabain, monensin or veratridine, all of which increase intracellular sodium concentrations, reduced myo-[3H]inositol uptake, whereas dinitrophenol, potassium cyanide and carbonyl cyanide m-chlorophenyl hydrazone were without effect. Substance P affected only the sodium-dependent uptake process of myo-[3H]inositol, this inhibitory effect requiring extracellular calcium. Similar observations were made with the muscarinic agonist carbachol. From these results, an increase in intracellular sodium concentration linked to the activation of calcium-sensitive cation-permeant channels appears to be responsible for the inhibitory effects of substance P and carbachol on myo-[3H]inositol uptake, these effects being mediated respectively by NK1 and muscarinic receptors coupled to a phospholipase C.

Animals↗
PubMed1991

Distinct presynaptic regulation of dopamine release through NMDA receptors in striosome- and matrix-enriched areas of the rat striatum.

Striosome- and matrix-enriched striatal zones were defined in coronal and sagittal brain sections of the rat, on the basis of 3H-naloxone binding to mu-opiate receptors (a striosome-specific marker). Then, using a new in vitro microsuperfusion device, the NMDA (50 microM)-evoked release of newly synthesized 3H-dopamine (3H-DA) was examined in these four striatal areas under Mg(2+)-free conditions. The amplitudes of the responses were different in striosomal (171 +/- 6% and 161 +/- 5% of the spontaneous release) than in matrix areas (223 +/- 6% and 248 +/- 12%), even when glycine (1 or 100 microM) was coapplied (in the presence of 1 microM strychnine). In the four areas, the NMDA-evoked release of 3H-DA was blocked completely by Mg2+ (1 mM) or (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801; 1 microM) and almost totally abolished by kynurenate (100 microM). Because the tetrodotoxin (TTX)-resistant NMDA-evoked release of 3H-DA was similar in striosome- (148 +/- 5% and 152 +/- 6%) or matrix-enriched (161 +/- 5% and 156 +/- 7%) areas, the indirect (TTX-sensitive) component of NMDA-evoked responses, which involves striatal neurons and/or afferent fibers, seems more important in the matrix- than in the striosome-enriched areas. The modulation of DA release by cortical glutamate and/or aspartate-containing inputs through NMDA receptors in the matrix appears thus to be partly distinct from that observed in the striosomes, providing some functional basis for the histochemical striatal heterogeneity.

Animals↗
PubMed1991

Inhibitory influence of the mesocortical dopaminergic neurons on their target cells: electrophysiological and pharmacological characterization.

Both dopaminergic (DA) and noradrenergic (NA) systems exert an inhibitory influence on the activity of prefrontal cortical neurons (PFC). As NA-containing fibers run close to the dorsal ventral tegmental area (VTA), electrical stimulation of the VTA might coactivate both DA and NA systems. In the present study extracellular recordings and microiontophoresis were used in anesthetized rats to analyze first whether the inhibitory cortical responses to VTA stimulation and DA application were mediated by DA or adrenergic receptors. Inhibitory responses elicited by DA application or VTA stimulation were observed in PFC output neurons identified by antidromic activation from subcortical structures. Both types of inhibitory effects were reversed by the DA antagonist sulpiride, but not by the adrenergic antagonists prazosin (alpha-1), yohimbine (alpha-2) or propranolol (beta). NA and the beta agonist isoproterenol inhibited the activity of PFC cells and these effects were antagonized by propranolol, but neither by prazosin and yohimbine nor by the DA antagonist sulpiride. Thus, the inhibitory influence of the mesocortical DA system in the PFC involves DA, but not NA, recognition sites. The DA receptor subtype mediating the inhibitory effects of VTA stimulation and DA application in the PFC was analyzed further. VTA- and DA-evoked inhibitory responses were antagonized by the D2 selective antagonists (-)-sulpiride, LUR 2366 and RIV 2093, but not by the D1 selective antagonist SCH23390. In addition, the DA-induced inhibitory response was mimicked by the selective D2 agonist LY 171555 but not by the selective D1 agonist SKF 38393. Surprisingly, haloperidol, which is also a potent D2 antagonist, failed to consistently block DA- and VTA-induced inhibitory effects. The present results indicate that the inhibition of PFC cells by mesocortical DA neurons is mediated via a subtype of DA receptors which is particularly sensitive to benzamides.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Evidence for phosphatidylinositol anchorage of opioid binding proteins in rat brain.

Treatment of rat brain sections and of thalamic and striatal membranes with phosphatidylinositol phospholipase C (PIPLC), an enzyme known to hydrolyse only phosphatidylinositol and its derivatives, significantly alters the specific binding of mu- and delta-opioid ligands on their receptors. These results suggest that some opioid binding proteins are membrane-anchored by a glycosylphosphatidylinositol (GPI) linkage.

Animals↗
PubMed1990

Dopamine-induced homologous and heterologous desensitizations of adenylate cyclase-coupled receptors on striatal neurons.

Striatal neurons in primary culture express a wide variety of adenylate cyclase-coupled receptors, and particularly dopamine (DA) D1 receptors, which are known to induce an increase in cyclic AMP production. To study desensitization of those receptor-mediated responses, neurons were incubated in the presence of saturating concentrations of DA for various times. We observed a rapid desensitization of the D1 response after 15 min, which reached a maximum after 18 h. This effect is reversible since incubation of treated neurons in fresh medium led to a complete recovery of the dopamine response within 2 days. In addition, a brief treatment with DA resulted in heterologous desensitization of beta-adrenoceptors and 5-HT and vasoactive intestinal peptide (VIP) receptors coupled to adenylate cyclase on striatal neurons. Similar to what was observed for homologous desensitization, these effects are obtained within the first 15 min of exposure to DA; however, they are short-lasting, even in the persistent presence of DA.

Adenylyl Cyclases↗
PubMed1990

Inhibition of spontaneous and evoked unit activity in the rat medial prefrontal cortex by mesencephalic raphe nuclei.

The rat medial prefrontal cortex (PFC) receives a serotoninergic (5-HT) innervation which originates from the mesencephalic raphe nuclei. In the present study we determined the influence of the 5-HT ascending systems on the spontaneous and evoked activity of PFC neurons in anesthetized rats. Stimulation of the dorsal (DRN) and of the median raphe (MRN) nuclei inhibited the spontaneous activity of 35.0% and 52.8% of the PFC cells tested (mean duration of the inhibition: 75.5 and 82.2 ms, respectively). These inhibitory responses are likely mediated by the 5-HT-containing neurons since they were decreased markedly following selective destruction of ascending 5-HT pathways induced by local injections of 5,7-dihydroxytryptamine. Moreover, the inhibitory effect of MRN stimulation could be blocked by systemic administration of the 5-HT2 receptor antagonists: ketanserin and ritanserin. The effects of MRN stimulation on two types of evoked responses were studied. The excitatory responses of PFC neurons induced by the stimulation of the mediodorsal nucleus of the thalamus (MD) were inhibited by MRN stimulation applied before that of MD. Similarly, the activation of PFC cells induced by a noxious tail pinch was suppressed by a concomitant stimulation of the MRN. These results indicate that 5-HT neurons exert an inhibitory control on spontaneous or evoked activity in the rat PFC.

5,7-Dihydroxytryptamine↗
PubMed1990

In vitro effects of 17 beta-oestradiol on the sensitivity of receptors coupled to adenylate cyclase on striatal neurons in primary culture.

Pretreatment of intact striatal neurons from the mouse embryo in primary culture with 17 beta-oestradiol (10(-9) M), 24 hours) enhanced the stimulation of adenylate cyclase activity induced by either dopamine (D1 receptors), isoproterenol, serotonin or 2-chloroadenosine (maximal effective concentrations) but suppressed inhibitory responses evoked by agonists of D2-dopaminergic or enkephalin (mu and delta) receptors. Binding studies indicated that some of these effects are (beta 1) or are not (D1 and D2) associated with changes in the number of receptors. Similar effects were partially seen with testosterone but not with 17 alpha-oestradiol, progesterone or dexamethasone and those induced by 17 beta-oestradiol were abolished when cells were exposed to inhibitors of mRNA transcription (alpha-amanitin) or protein synthesis (cycloheximide). Modifications in the properties of Gs or Go,i proteins were postulated because the number of adenylate cyclase catalytic subunits was not affected by 17 beta-oestradiol pretreatment. Results of ADP-ribosylation experiments with cholera toxin or pertussis toxin and of immunoblot experiments with anti-G alpha o and anti-G beta sera led us to suggest that 17 beta-oestradiol induces qualitative modifications in Go,i proteins leading to a stabilization of the associated form of the heterotrimer G alpha o,i beta gamma. In fact, pretreatment with pertussis toxin (which impairs G alpha o,i beta gamma dissociation) mimics the effects of 17 beta-oestradiol on responses of adenylate cyclase to stimulatory and inhibitory agonists.

Adenylyl Cyclases↗
PubMed1990

Respective contributions of neuronal activity and presynaptic mechanisms in the control of the in vivo release of dopamine.

Studies performed in several in vivo and in vitro conditions have demonstrated that the release of dopamine from nerve terminals of the nigrostriatal dopaminergic neurons depends not only on the activity of dopaminergic cells but also on presynaptic regulations by heterologous fibers. The presynaptic facilitation of dopamine release by the cortico-striatal glutamatergic neurons has been particularly investigated. A quisqualate/kainate receptor subtype is involved in the direct (tetrodotoxine-resistant) presynaptic regulation of dopamine release by glutamate. The respective roles of presynaptic events and nerve activity in the control of dopaminergic transmission are discussed.

Animals↗
PubMed1990

Striatal opiate mu-receptors are not located on dopamine nerve endings in the rat.

In rat striatal slices, the autoradiographic analysis of [3H]naloxone binding allows one to define highly labelled patches corresponding to the striosomes and representing about 17% of the total striatal volume, surrounded by a poorly labelled zone, the matrix. Previous studies have shown that the density of these mu-opiate receptor binding sites is decreased by about 28% following destruction of the striatal dopamine innervation suggesting a partial localization of these receptors on dopamine presynaptic nerve endings. These results were confirmed but, in addition, we have shown that a chronic (30 days) blockade of dopamine transmission obtained by treatment of the animals with a long acting neuroleptic induces a similar decrease of mu binding sites. Further experiments made with D-Pen2,D-Pen5-[tyrosyl-3-5(n)-3H] enkephalin, a selective delta opiate receptor agonist, have revealed that the density of delta opiate binding sites is decreased (30%) in rats with striatal dopamine denervation but not in those treated with the long acting neuroleptic. These data indicate that part of these delta receptors is located on dopamine nerve terminals but are not in favour of the presence of mu receptors on these nerve terminals. The decrease in [3H]naloxone binding sites induced by prolonged interruption of dopamine transmission can be attributed to postsynaptic events.

Animals↗