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Biomedical subjects

J Glowinski

Publications and source records attributed to J Glowinski.

At least 361 records · Page 20Linked to original sources
PubMed1981

[3H]Metergoline: a new ligand of serotonin receptors in the rat brain.

A specific binding site for [3H]metergoline characterized by a KD of 0.5-1.0 nM was detected in microsomal and synaptic plasma membranes from various areas of the adult rat brain. Experiments with 5,7-dihydroxytryptamine- and kainic acid-induced lesions indicated that this specific binding site was localized post-synaptically with respect to serotoninergic neurons. The pharmacological characteristics of [3H]metergoline binding to microsomal membranes from the whole forebrain strongly suggest that this ligand labels a class of serotonin receptors. This was particularly obvious in the hippocampus in which serotonin was about 400 times more potent than dopamine and noradrenaline for displacing bound [3H]metergoline. In the striatum, serotonin was only 10 times as potent as dopamine in inhibiting [3H]metergoline binding, suggesting that this ligand may also bind to dopamine receptors. Striking similarities between the binding sites for [3H]metergoline and [3H]serotonin were observed in the hippocampus. Thus, not only the total numbers of binding sites for these two ligands in control rats but also their respective increases following intracerebral 5,7-dihydroxytryptamine treatment were very similar. Therefore, at least in the hippocampus, [3H]metergoline might well be the appropriate ligand for studying the characteristics of the 'antagonist form' of serotonin receptors postulated by Bennett and Snyder.

5,7-Dihydroxytryptamine↗
PubMed1981

In vivo release of transmitters in the cat basal ganglia.

The release of transmitters was studied in various structures of the basal ganglia in cats implanted with several push-pull cannulas. Local depolarization enhanced Met-enkephalin release in the globus pallidus. Activation of striatonigral substance P(SP) neutrons stimulated the transmitter release from terminals. Unilateral electrical stimulation of the caudate nucleus evoked GABA release in both substantia nigrae and pallidoentopeduncular nuclei. The unilateral facilitation or interruption of nigral SP transmission modified dopamine (DA) release in the ipsilateral caudate nucleus in contrast, modifications of GABAergic or glycinergic nigral transmissions induced bilateral symmetrical effects, whereas bilateral asymmetrical changes in DA release in the two caudate nuclei were seen during the unilateral modification of nigral DA transmission. Changes in the dendritic release of DA induced changes in serotonin release both in the substantia nigra and in the ipsilateral caudate nucleus. Finally, it will be shown that acetylcholinesterase can be released from the substantia nigra and the caudate nucleus through processes dependent on nerve activity.

Acetylcholinesterase↗
PubMed1981

[Angiotensin II and nigostriatal system (author's transl)].

The central renin-angiotensin system is implicated most importantly in the control of water balance, blood pressure and endocrine function (AVP and ACTH). Several central structures are sensitive to angiotensin II (A II), principally: the subfornical organ, the vascular organ of the lamina terminalis, the area postrema and the preoptic area. Furthermore, binding studies with radio-active ligands and also immunohistofluorescence have shown respectively the presence of A II receptors and immunoreactive material bound by A II antibodies in other central structures, and in particular parts of the motor system. In the present study, a double approach, both electrophysiological and biochemical, was used to investigate the possible role of the peptide A II in the neostriatum of the rat. 1 Microiontophoretic application of A II was shown to modify the spontaneous activity of some neurones (15/68) in the neostriatum. Generally, the action of A II was inhibitory and the inhibition was blocked by Sar1-Ileu8-A II, a specific A II antagonist. 2 Angiotensin II 10(-6) M; 10(-5) M; 5.10(-5) M) stimulated the spontaneous release of 3H-dopamine continuously synthetized from 3H-tyrosine in striatal slices of the rat. The A II-evoked release of 3H-dopamine was prevented when slices were superfused with a calcium-free medium containing EGTA. It was also suppressed in the presence of the specific antagonist Sar1-Ileu8-A II. 3 Kainic acid lesion of the intrastriatal cell bodies produced a moderate decrease of A II in the striatum (38%) whilst the activity of the converting enzyme decreased dramatically (-68%). These results suggest that there are angiotensin-containing nerve endings in the neostriatum, and that the cell bodies of such nerves are located outside this structure. Their functional role is discussed.

Angiotensin II↗
PubMed1981

Control of 5-HT release in the caudate nucleus and the substantia nigra of the cat.

The release of 3H-5-HT newly synthesized from 3H-tryptophan was measured in the caudate nucleus (CN), the substantia nigra (SN) and the dorsal raphe nucleus (DR) of cats slightly anaesthetized with halothane. It was observed that: 1. 3H-5-HT release was 2.5 and 3.2 times higher in the DR than in the SN and the CN respectively; 2. Cooling (0 degrees C) of the DR by the use of a cryoelectrode resulted in a decrease in 3H-5-HT release in both the CN and SN; 3. Application of 5-HT (10(-7) M) into the DR induced a local increase in 3H-5-HT release, while decreasing 3H-5-HT release in the CN and SN; 4. Conversely, the blockade of 5-HT receptors in the DR by metergoline (10(-6) M) decreased the local release of 3H-5-HT and increased 3H-5-HT release in the CN. No effect was observed in the SN. These results suggest that 5-HT releases into the DR may control the activity of serotoninergic neurons.

Animals↗
PubMed1980

Effect of striatal cells on in vitro maturation of mesencephalic dopaminergic neurones grown in serum-free conditions.

It is well documented that target cells can regulate the morphological and biochemical development of peripheral afferent neurones, but little is known about the existence of such regulatory mechanisms in the central nervous system. We therefore investigated previously the influence of striatal target cells on the maturation in vitro of nigrostriatal dopaminergic neurones, which survive in culture for more than 5 weeks, develop dense arborizations and both take up 3H-dopamine (DA) by a high-affinity specific process and synthesize 3H-DA from 3H-tyrosine. Furthermore, depolarization by potassium or veratridine stimulates the release of DA through a calcium-dependent mechanism and tetrodotoxin prevents the veratridine-evoked release of the transmitter. Both the number of 3H-DA uptake sites and the capacity for 3H-DA synthesis were at least doubled when the neurones were cultured with target cells from the striatum. To determine whether glial cells which proliferate in serum-complemented medium are partly responsible for the maturation of dopaminergic neurones and/or for the effect of striatal cells, we have now repeated the experiment using serum-free medium in which virtually pure neuronal populations can be obtained. The reduction in the number of glia did not affect either the maturation of dopaminergic cells alone, or the effect of striatal cells. Autoradiographic analysis of the number of dopaminergic cells strongly suggests that the stimulatory effect is related to increased capacities of 3H-DA uptake and synthesis per dopaminergic neurone.

Animals↗
PubMed1980

In vivo release of endogenously synthesized [3H]GABA from the cat substantia nigra and the pallido-entopeduncular nuclei.

Halothane anesthetized cats were implanted with push--pull cannulae to study the release of [3H]GABA continuously formed from [3H]glutamine in the substantia nigra (SN) and in the pallido-entopeduncular nuclei (PEP). A spontaneous release of [3H]GABA was observed from both structures and it reached a steady state level 1 h after the beginning of the superfusion with [3H]glutamine. In cats implanted with two push--pull cannulae, the local application of potassium (47 mM) in the PEP stimulated the release of [3H]GABA from the ipsilateral SN. In cats implanted with 4 push--pull cannulae, the unilateral 10 min electrical stimulation of the caudate nucleus evoked the release of [3H]GABA not only from the ipsilateral SN, but also in most cases from the contralateral structure. This stimulus also enhanced the release of [3H]GABA from PEP but the effects were mainly observed in the medio-caudal part of the ipsilateral PEP and in the latero-rostral part of the contralateral structure. In all cases, the changes in [3H]GABA release were observed during and after the electrical stimulation. The ipsilateral effects can be attributed to the direct activation of the caudato-PEP or caudato-SN GABAergic neurons. A polysynaptic neuronal loop must be involved in the symmetric contralateral effects.

Animals↗
PubMed1980

Dopamine released from dendrites in the substantia nigra controls the nigral and striatal release of serotonin.

Using push--pull cannulae, the release of endogenously synthesized [3H]serotonin was estimated in both substantia nigra and caudate nuclei of 'encéphale isolé' cats. The unilateral nigral application of dopamine (10(-7) M) reduced [3H]serotonin release in ipsilateral structures whereas alpha-methylparatyrosine (10(-4) M) induced opposite effects. Both treatments decreased [3H]serotonin release in the contralateral caudate nucleus but not in the contralateral substantia nigra. As a working hypothesis it is suggested that the effects observed are related to changes in the activity of nigroraphe neurons regulated by dopamine release from dendrites of the nigrostriatal dopaminergic neurons. However it cannot yet be excluded that the local changes in [3H]serotonin release induced by the nigral application of dopamine or alpha-methylparatyrosine result from presynaptic modulation.

Animals↗