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J Glowinski

Publications and source records attributed to J Glowinski.

At least 253 records · Page 14Linked to original sources
PubMed1986

Opposite effects of sulfated cholecystokinin on DA-sensitive adenylate cyclase in two areas of the rat nucleus accumbens.

The nucleus accumbens of the rat receives a mixed DA/CCK8 innervation in its posterior part while its anterior part is innervated by distinct DA and CCK8 fibres. In vitro, the addition of CCK8 (0.3-1 microM) potentiated the activating effect of DA (10-30 microM) on adenylate cyclase in tissue homogenates obtained from the posterior part of the nucleus accumbens, whilst this activating effect was reduced by CCK8 in the anterior part. These results suggest the existence of two types of regulation of the D1 receptor by CCK8 depending on the identity (mixed or not mixed) of their innervating fibres.

Adenylyl Cyclases↗
PubMed1986

Enhancement of glutamate release in the rat striatum following electrical stimulation of the nigrothalamic pathway.

The release of unlabelled amino acids and newly synthesized [3H]dopamine was estimated in the striatum of halothane-anaesthetized rats superfused using a push-pull cannula. Electrical stimulation of the substantia nigra pars reticulata (SNR), enhanced the release of glutamate (maximal effect +51%) in the ipsilateral striatum. The outflow of [3H]dopamine, aspartate, serine and glutamine was unchanged. Seven-12 days after electrolytic lesion of the ipsilateral ventromedial nucleus of the thalamus SNR, stimulation no longer increased the striatal release of glutamate. It is suggested that electrical stimulation of the SNR enhances the striatal release of glutamate, presumably originating from corticostriatal fibres, by activating a nigrothalamocortical polysynaptic pathway.

Animals↗
PubMed1986

Effects of ventro-medial mesencephalic tegmentum (VMT) stimulation on the spontaneous activity of nucleus accumbens neurones: influence of the dopamine system.

The effects of VMT-stimulation (100-500 microA, 0.6 ms; 1 Hz) on the spontaneous activity of neurones in the nucleus accumbens were analyzed in ketamine-anaesthetized rats. On spontaneously active cells (firing greater than 0.5 spikes/s), 3 types of responses were observed: either inhibition (36%), excitation (5%) or a composite sequence of excitation followed by inhibition (12%). Moreover, 14% of silent nucleus accumbens neurones were excited by single pulse VMT-stimulation. Finally, 3% of nucleus accumbens neurones recorded were driven antidromically by VMT-stimulation. Destruction of dopamine (DA) projections by 6-hydroxydopamine prevented the inhibitory responses to VMT stimulation in the great majority of cells studied, without affecting the excitatory responses. After systemic administration of haloperidol or sulpiride, the inhibitory responses to VMT stimulation were attenuated markedly, whilst the excitatory responses were, however, maintained. These results suggest that the inhibitory, but not the excitatory, effects of VMT-stimulation on nucleus accumbens neurones may be mediated by an activation of the mesolimbic DA system.

Animals↗
PubMed1986

Stimulatory effect of substance P on the spontaneous release of newly synthesized [3H]dopamine from rat striatal slices: a tetrodotoxin-sensitive process.

Striatal slices from the rat were continuously superfused with [3H]tyrosine in order to estimate the release of newly synthesized [3H]dopamine [( 3H]DA). Substance P (SP) and neuromedin K (NKB) stimulated the spontaneous release of [3H]DA when used in concentrations (from 10(-9) M to 10(-7) M). The stimulatory effect of substance P (10(-8) M) was prevented completely when slices were superfused with tetrodotoxin (10(-7) M) or the substance P antagonist (D-Arg1,D-Pro2,D-Trp7,9,Leu11) substance P (10(-5 M) indicating that the response evoked by substance P was mediated by substance P receptors but that these were not located on DA nerve terminals. In addition, substance P did not modify the stimulatory effect of acetylcholine (ACh) (10(-5) M) on the spontaneous release of [3H]DA since the effects of substance P (10(-7) M) and ACh (10(-5) M) were additive.

Acetylcholine↗
PubMed1986

Two simian virus 40 (SV40)-transformed cell lines from the mouse striatum and mesencephalon presenting astrocytic characters. II. Interactions with mesencephalic neurons.

In an accompanying paper we report the characterization on the basis of pharmacological and immunological criteria of two astrocytic cell lines originating from the rostral mesencephalon and the striatum of the embryonic mouse (F7-Mes and F12-Str). This report compares the interactions of primary mesencephalic neurons with the astrocytic clones to that displayed with either an SV40-transformed fibroblastic clone (BT2) or primary mesencephalic (G-Mes) and striatal (G-Str) astrocytes. We show that BT2 differs from all other cell types (F7-Mes, F12-Str, G-Mes and G-Str). Indeed, as opposed to these cells BT2 is a poor substratum for neuronal adhesion or neuritic growth. This was clearly demonstrated by morphological examination of cocultures of the tested cells with either mesencephalic explants or dissociated cells. In addition a statistical analysis is provided which only concerns the dopaminergic (DA) neurons visualized by autoradiography after specific uptake of [3H]DA. The number of DA cells attached, the total length of their neurites and the degree of branching behaviour were examined. With the help of these criteria we show that F7-Mes and F12-Str are very similar to primary astrocytes and differ highly significantly from BT2. However, although sharing the main astrocytic features, F7-Mes and F12-Str do not differ from one another in their ability to induce the branching of DA neurites as their non-transformed counterparts do.

Animals↗
PubMed1986

Two simian virus 40 (SV40)-transformed cell lines from the mouse striatum and mesencephalon presenting astrocytic characters. III. A light and electron microscopic study.

In two preceding papers we described the cloning of two astrocytic cell lines by simian virus 40 (SV40) transformation of embryonic mouse mesencephalon (F7-Mes) and striatum (F12-Str). The characterization of these lines as belonging to the astrocytic lineage is based on pharmacological, immunocytochemical and physiological data. Here we present quantitative and qualitative data on the morphological aspects of these two astrocytic clones observed under light and electron microscopy. We show that the clones present ultrastructural characters reminiscent of the morphology of young astrocytes. On one hand, they are rather similar to primary astrocytes in culture; on the other, they differ both from a clonal fibroblastic cell line (BT2) and from embryonic mouse fibroblasts in primary culture. These astroblastic clones display 4 morphologically different cell populations which we called types I, II, III and IV. Types II and III are very similar and represent the most predominant cells; their morphologies strongly remind of that of astroblasts. Type I corresponds to glioblasts and does not account for more than 15-20% of the total population. Type IV, which is very similar to differentiated velamentous astrocytes, normally represent ca. 5% of the cells. However, when the transformed cells are treated with mitomycin or mitomycin + dibutyryl cyclic AMP (dbcAMP), the proportion of type IV cells increases very much (up to more than 50% of the cells) while types I, II and III become less numerous. Morphological analysis therefore confirms that the two cell lines derived from the SV40 transformation of 14-day-old embryonic mesencephalic and striatal cells belong to the astrocytic lineage. Moreover, it seems that they can differentiate in vitro in cell culture conditions either spontaneously or under the action of pharmacological treatments known to enhance normal astrocyte maturation.

Animals↗
PubMed1986

Quantitative autoradiographic analysis of the distribution of binding sites for [125I]Bolton Hunter derivatives of eledoisin and substance P in the rat brain.

[125I]Bolton and Hunter eledoisin binds to a single class of non-interacting sites in rat cerebral cortex tissue sections with an apparent Kd of 9.9 nM and a Bmax of 244 fmol/mg protein. When concentrations of up to 23 nM [125I]Bolton and Hunter eledoisin were used, [125I]Bolton and Hunter eledoisin binding was specific, saturable and reversible. Kassinin, eledoisin and neurokinin B were more potent than substance P and neurokinin A in inhibiting the specific binding of [125I]Bolton and Hunter eledoisin to cerebral cortex tissue sections. These kinetic and pharmacological characteristics are consistent with results obtained from binding studies on cortical synaptosomes. When the localization of [125I]Bolton and Hunter substance P and [125I]Bolton and Hunter eledoisin binding sites were compared, differences in many areas of the brain were noted. Large differences were seen in the paraventricular and supraoptic hypothalamic nuclei, and in layers IV and V of the cerebral cortex, which were densely labeled by [125I]Bolton and Hunter eledoisin, but not by [125I]Bolton and Hunter substance P. In contrast, nuclei of the septum (diagonal band of Broca, septohippocampal nucleus, dorsal part of the lateral septal nucleus), the rostrodorsal part of the hippocampus and other discrete nuclei [endopyriform nucleus, anterior cortical amygdaloid nucleus, the vermis columns (9-10), the dorsal tegmental nucleus, the hypoglossal and ambiguus nucleus] had high levels of [125I]Bolton and Hunter substance P binding but were only labeled weakly by [125I]Bolton and Hunter eledoisin. Thus, the two ligands seem to label different sites, since these binding sites have different biochemical and pharmacological properties, and are localized in different anatomical structures.

Animals↗
PubMed1986

In vivo presynaptic control of dopamine release in the cat caudate nucleus--I. Opposite changes in neuronal activity and release evoked from thalamic motor nuclei.

Halothane-anaesthetized cats implanted with three push-pull cannulae were used to estimate the effects of gamma-aminobutyric acid (GABA) application (either 10(-3) M or 10(-5) M) into the left motor nuclei of the thalamus (either ventralis medialis, or ventralis lateralis) on the firing rate of dopamine cells in the left substantia nigra (caudomedial part) and on the release of [3H]dopamine continuously synthesized from [3H]tyrosine, in the left substantia nigra (caudomedial part) and the left caudate nucleus. Preliminary experiments were performed to establish the electrophysiological characteristics of dopamine cells and non-dopamine cells in the pars compacta (mediocaudal part of substantia nigra) in groups of animals with the electrode inserted within the nigral push-pull cannula or with the electrode inserted in the absence of a push-pull cannula. Dopamine and non-dopamine cells were distinguished according to several criteria (shape of the spike, duration of spike, frequency of discharge, conduction velocity estimated following antidromic activation from the caudate nucleus for dopamine cells or from the ventralis medialis for non-dopamine cells). Data obtained from recordings made within the push-pull cannula were identical to those obtained in the absence of the cannula. In addition both the intravenous injection of amphetamine or its local application (10(-6) M) in the substantia nigra inhibited the firing rate of dopamine cells. When GABA was applied at 10(-3) M for 30 min into the ventralis medialis-ventralis lateralis the multi-unit activity of thalamic cells recorded within the push-pull cannula was inhibited. Single unit activity of dopamine cells was also inhibited and [3H]dopamine release was reduced in the caudate nucleus and increased in the substantia nigra. These results suggest that under these conditions, dopamine release from nerve terminals depended upon nerve activity and that dopamine released from dendrites inhibited the activity of dopamine cells. When GABA was applied at 10(-5) M for 30 min into the ventralis medialis-ventralis lateralis, multi-unit activity of thalamic cells was increased, single-unit activity of dopamine cells was inhibited and [3H]dopamine release was enhanced in the ipsilateral caudate nucleus and not affected in the left substantia nigra, demonstrating that in this situation the release of dopamine from nerve terminals was not dependent on the firing rate of dopamine cells. In addition, these results indicated that the activity of dopamine cells was not always dependent on the dendritic release of dopamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

In vivo presynaptic control of dopamine release in the cat caudate nucleus--II. Facilitatory or inhibitory influence of L-glutamate.

The local effects of various concentrations of L-glutamate (from 10(-8) M up to 10(-3) M) on the release of [3H]dopamine synthesized continuously from [3H]tyrosine were examined in the caudate nucleus of halothane-anaesthetized cats implanted with push-pull cannulae. When used at a concentration of 10(-8) M or 10(-7) M, L-glutamate stimulated the release of [3H]dopamine from nerve terminals of the nigrostriatal dopamine neurons. This effect was still observed in the presence of tetrodotoxin (5 X 10(-7) M) but it was antagonized by 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M), an antagonist dopamine nerve terminals. While no significant change in the release of [3H]dopamine was observed with 10(-6) M L-glutamate, higher concentrations (from 10(-5) M to 10(-3) M) of the amino acid produced a long-lasting reduction in the [3H]transmitter release. This latter effect was also antagonized by PK 26124 (10(-5) M) but, unlike that observed with 10(-8) M L-glutamate, it did not persist in the presence of tetrodotoxin (5 X 10(-7) M). On the contrary, a marked stimulation of the release of [3H]dopamine was seen in the presence of this neurotoxin. The reduction in the release of [3H]dopamine produced by 10(-4) M L-glutamate was also antagonized by bicuculline (10(-5) M) and moreover a marked stimulation of [3H]dopamine release took place in the presence of this gamma-aminobutyric acid (GABA) antagonist. Therefore, high concentrations of L-glutamate exerted an inhibitory presynaptic control on [3H]dopamine release which seemed to be indirect and mediated partly by GABAergic neurons. Since a sustained reduction in the spontaneous release of [3H]dopamine was seen in the presence of PK 26124, the corticostriatal glutamatergic neurons appeared to exert a tonic facilitatory presynaptic influence on dopamine release. This effect was important since it represented 40% of the tetrodotoxin-sensitive release of the [3H]transmitter. The direct (stimulatory) and indirect (inhibitory) presynaptic controls on dopamine release mediated by corticostriatal glutamatergic fibres are discussed in light of previous findings and of the anatomical organization of the caudate nucleus.

Animals↗
PubMed1986

In vivo presynaptic control of dopamine release in the cat caudate nucleus--III. Further evidence for the implication of corticostriatal glutamatergic neurons.

In confirmation of previous results, experiments in halothane-anaesthetized cats implanted with push-pull cannulae showed that the unilateral application of GABA (10(-5) M for 30 min) into the left thalamic motor nuclei (either ventralis medialis, or ventralis lateralis) markedly stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both caudate nuclei and in the contralateral substantia nigra. Three types of experiments confirmed that the changes in [3H]dopamine release evoked in both caudate nuclei resulted from a presynaptic facilitation mediated by the bilateral corticostriatal glutamatergic projection: The constant delivery of 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M) to the left caudate nucleus prevented the increased release of [3H]DA evoked by application of gamma-aminobutyric acid (GABA) (10(-5)M) into ventralis medialis-ventralis lateralis while an enhanced release of [3H]dopamine still occurred in the contralateral caudate nucleus. Since PK 26124 is an antagonist of glutamatergic transmission, the presynaptic facilitation may involve glutamatergic neurons. Single unit recordings of dopamine cells in the contralateral substantia nigra indicated that the increased release of [3H]dopamine from dendrites evoked by the application of GABA (10(-5)M) into ventralis medialis-ventralis lateralis was associated with a reduction in the firing rate of dopamine cells. Thus, the enhanced release of [3H]dopamine in the contralateral caudate nucleus may involve a presynaptic facilitatory process. Finally, the unilateral lesion of the sensory motor cortex made prior to the superfusion of caudate nucleus with [3H]tyrosine prevented the responses evoked in the two caudate nuclei by the application of GABA (10(-4) M) into ventralis medialis-ventralis lateralis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

In vivo release of [3H]gamma-aminobutyric acid in the rat neostriatum--I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents.

The release of [3H]gamma-aminobutyric acid continuously synthesized from [3H]glutamine was studied in the striatum of halothane-anaesthetized rats superfused with a push-pull cannula. The levels of spontaneously released [3H]GABA were identical in all striatal regions examined, but were found to be higher at the junction between the striatum and the globus pallidus. Superfusion with a medium enriched in K+ ions induced a concentration-dependent increase in [3H]GABA release. Superfusion with a Ca2+-free medium did not affect the spontaneous outflow of [3H]GABA but sharply reduced the release of [3H]GABA evoked by 30 mM K+. Locally applied tetrodotoxin (50 microM) decreased slightly the spontaneous release of [3H]GABA (-22%). When acetylcholine (50 or 500 microM) was added to a superfusion medium containing eserine (50 microM), the spontaneous release of [3H]GABA was enhanced in the ventral but not in the dorsal region of the striatum. The local application of 2,3,4,5-tetrahydro, 7,8,-dihydroxy, 1-phenyl, 1-H, 3-benzazepine (10 microM), a dopaminergic agonist acting preferentially on D1 receptors increased the release of [3H]GABA in the dorsal striatum (+32%) but decreased it slightly (-19%) in the ventral striatum. 3-(2-(N-3 hydroxyphenylethyl)N-propylamino)ethyl-phenol (50 microM), a preferential D2 receptor agonist, decreased [3H]GABA release when it was applied dorsally (-23%) but not ventrally in the striatum. It is concluded that the regulation of the release of [3H]GABA by acetylcholine and dopaminergic drugs is different in the dorsal and ventral regions of the striatum. These differences may be related to the existence of subpopulations of GABA neurons and may well have functional implications as suggested by behavioural studies.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

In vivo release of [3H]gamma-aminobutyric acid in the rat neostriatum--II. Opposing effects of D1 and D2 dopamine receptor stimulation in the dorsal caudate putamen.

The effects of several dopaminergic agonists and antagonists on the spontaneous release of [3H]gamma-aminobutyric acid were investigated in the dorsal striatum of halothane-anaesthetized rats. A push-pull cannula was implanted and the tissue was superfused continuously with a physiological medium containing [3H]glutamine, the precursor of [3H]GABA. Drugs were added to the superfusion medium. 2-Amino,6,7-dihydroxy,1,2,3,4-tetrahydro-naphtalene (ADTN, a mixed D1 and D2 receptor agonist) and D-amphetamine (a drug that enhances the release of endogenous dopamine) increased the release of 3H-GABA. The effect of ADTN was blocked by a D1 antagonist [R-(+),8-chloro, 7-hydroxy,2,3,4,5-tetrahydro,3-methyl,5-phenyl,1-H,3-benzazepine (SCH 23390)] but not by a D2 antagonist (S-sulpiride). Furthermore the stimulation of D1 receptors either by 2,3,4,5-tetrahydro,7,8-dihydroxy,1-phenyl,1-H,3-benzazepine or by D-amphetamine in the presence of S-sulpiride also enhanced the release of [3H]GABA. On the other hand, a selective D2 receptor agonist (3-(2-(N-3-hydroxy-phenylethyl)N-propylamino)ethyl-phenol) decreased the release of [3H]GABA. This effect was blocked in the presence of S-sulpiride. By itself the D1 receptor antagonist (SCH 23390) decreased the release of [3H]GABA whereas the D2 receptor antagonist (S-sulpiride) had no effect. It was concluded that stimulation of D1 and D2 receptors produces opposing effects on the spontaneous release of [3H]GABA in the dorsal striatum. Stimulation of D1 receptors facilitates the release of [3H]GABA whilst stimulation of D2 receptors inhibits it. The effect of D1 receptor stimulation appears to be predominant, and endogenous dopamine may activate tonically the release of GABA through these receptors in our experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Release of newly synthesized 3H-dopamine in the striatum: an adaptation of the push-pull cannula method to awake restrained and anesthetized rats.

The release of newly synthesized 3H-dopamine (3H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in 3H-tyrosine. The level of spontaneous 3H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10(-6) M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of 3H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10(-5) M) or acetylcholine (5 X 10(-5) M) in the presence of eserine (5 X 10(-5) M) evoked respectively a fivefold and a 30% increase in spontaneous 3H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal 3H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat.

Acetylcholine↗
PubMed1986

Variation in the ability of neuroleptics to block the inhibitory influence of dopaminergic neurons on the activity of cells in the rat prefrontal cortex.

The stimulation of the ventro-medial mesencephalic tegmentum (VMT) induces an inhibition of the spontaneous activity of prefrontal cortical cells and blocks the excitatory responses evoked by the stimulation of the medio-dorsal nucleus of the thalamus (MD). This effect is mediated by the activation of the mesocortical dopaminergic (DA) system. In the present study, the influence of the systemic administration of several neuroleptics on the inhibition of prefrontal cortical cells induced by VMT stimulation has been analyzed in ketamine anaesthetised rats. The acute IP administration of fluphenazine (2 mg/kg), spiroperidol (2 mg/kg) or (+/-)sulpiride (100 mg/kg) reversed the inhibitory responses. Moreover, the number of cortical cells inhibited by VMT stimulation was considerably decreased after these treatments. Surprisingly, neither haloperidol at any dose used (0.1 to 0.5 mg/kg IV or 0.5 to 5 mg/kg IP) nor levomepromazine (25 mg/kg IP) nor the long acting neuroleptic, pipotiazine palmitic ester (32 mg/kg SC) blocked the inhibitory effect of VMT stimulation and in fact they lengthened the duration of the inhibition. Finally, the inhibition of MD evoked spikes in prefrontal cortical cells produced by VMT stimulation was no longer observed after sulpiride but persisted after haloperidol administration. Our findings confirm that the mesocortico-prefrontal DA neurons exert an inhibitory influence on target cells but they reveal differences in the efficacy of neuroleptics in blocking this effect.

Animals↗
PubMed1986

Apomorphine and haloperidol effects on striatal 3H-dopamine release in anesthetized, awake restrained and freely moving rats.

The ability of apomorphine (APO) and haloperidol (HAL) to affect the spontaneous release of newly synthesized 3H-DA in the striatum was studied in halothane anesthetized, gallamine paralyzed, awake restrained and freely moving rats. The striatum was continuously superfused through a push-pull cannula with a physiological medium enriched in 3H-tyrosine. Basal levels of 3H-DA release were different in the four experimental models: highest in halothane anesthetized rats, intermediate in awake restrained and gallamine treated rats and lowest in freely moving rats. In all experimental models IV or SC injection of APO (1 mg/kg) inhibited the release of 3H-DA (30-50%) from 15 to 90 min following its administration. In awake restrained and freely moving rats, stereotyped behaviour was observed for one hour following the APO injection. In halothane anesthetized rats the inhibitory effect of APO on 3H-DA release was prevented by pretreatment with HAL (2 mg/kg IV). Injection of HAL (2 mg/kg IV or SC) failed to enhance the release of 3H-DA in anesthetized and awake restrained rats, whilst a long-lasting increase in 3H-DA release was observed in gallamine treated and freely moving animals (55% and 120% respectively). However, catalepsy was observed in both restrained and freely moving rats. It is concluded that the modifications of 3H-DA release produced by HAL but not those produced by APO are dependent on the experimental model used, a fact possibly related to the different sites of action of these two drugs.

Anesthesia, General↗
PubMed1986

Dopaminergic control of 125I-labeled neurotensin binding site density in corticolimbic structures of the rat brain.

In the rat brain, destruction of dopaminergic cell groups by injections of 6-hydroxydopamine into the ventral mesencephalic tegmentum results in large decreases in the number of neurotensin binding sites in the mesencephalon and the striatum. In contrast, these lesions produce an increase in the number of 125I-labeled neurotensin binding sites in the lateral part of the prefrontal cortex despite a large decrease in cortical dopamine levels. Increases in the number of 125I-labeled neurotensin binding sites in this cortical area as well as in the entorhinal cortex, the nucleus accumbens, and the central part of the striatum were also obtained after chronic blockade of dopamine neurotransmission by a long-acting neuroleptic pipotiazine palmitic ester. We propose that dopamine inputs regulate the density of postsynaptic neurotensin binding sites through cortical and subcortical dopamine receptors. Therefore, some of the clinical effects of neuroleptics in schizophrenic patients could be partly related to changes in neurotensin neurotransmission.

Animals↗
PubMed1986

Substance P receptors in primary cultures of cortical astrocytes from the mouse.

Binding sites for substance P were labeled on intact cortical glial cells from newborn mice in primary culture using 125I-labeled Bolton-Hunter-labeled substance P. Maximal specific binding (95% of total binding) was reached after 2-3 weeks in culture. The binding was saturable, reversible, and temperature dependent. Scatchard and Hill analysis revealed a single population of noninteracting high-affinity binding sites (Kd, 0.33 nM; Bmax, 14.4 fmol per dish). Competition studies made with tachykinins and substance P analogues indicated that the characteristics of the 125I-labeled Bolton-Hunter labeled substance P binding sites on glial cells were identical to those on rat brain synaptosomes. 125I-labeled Bolton-Hunter labeled substance P binding sites were visualized by autoradiography, and differences in the intensity of labeling were seen among astrocytes. Substance P was found to stimulate phosphatidylinositol turnover; the EC50 value (0.36 nM) was identical to the IC50 value (0.38 nM) determined in binding studies. 125I-labeled Bolton-Hunter labeled substance P binding sites were also found on astrocytes derived from other brain structures and from the spinal cord of mice.

Animals↗