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Biomedical subjects

J Glowinski

Publications and source records attributed to J Glowinski.

At least 379 records · Page 21Linked to original sources
PubMed1980

Characteristics of serotonin receptors in the rat brain.

Two biochemical methods are currently available for studying 5-HT receptors in the central nervous system. The first consists of measuring the specific high affinity binding of 3H-5-HT to synaptic membranes. The other derives from the discovery of an adenylate cyclase which can be activated by 5-HT in brain homogenates. Whereas the specific 3H-5-HT binding is measurable in young as well as in adult rats, the 5-HT-sensitive adenylate cyclase can be quantitatively estimated only during the first three weeks following birth. Later on, the increment of adenylate cyclase activity produced by 5-HT is too low to permit valid measurements, notably in tissues from adult rats. Studies on the effects of various agonists and antagonists demonstrated that the specific binding site characterized by a high affinity for 3H-5-HT (Kd = 1.5 nM) exhibited the expected properties of a 5-HT receptor in brain. Performing chemical lesions on serotoninergic neurons by an intracerebral injection of 5, 7-dihydroxytryptamine or the blockade of central 5-HT receptors by the peripheral administration of methiothepin resulted in a subsequent increase in the number of specific binding sites for 3H-5-HT particularly in the hippocampus (+30 to +45%). In contrast, preliminary attempts to detect any supersensitivity of the 5-HT-sensitive adenylate cyclase after selective raphe lesions were unsuccessful. Indeed, several observations strongly suggested that the high affinity binding site for 3H-5-HT did not correspond to the 5-HT receptor coupled to adenylate cyclase in synaptic membranes: 1) the apparent affinity of the 5-HT-sensitive adenylate cyclase for 5-HT was about 300 times lower (Kd = 0.5 microM) than that of the specific 3H-5-HT binding site; 2)the ontogenic evolutions of 3H-5-HT binding and 5-HT-sensitive adenylate cyclase were not parallel, notably in the hippocampus; 3) they were differently affected by several drugs. For instance, quipazine, a putative 5-HT agonist, effectively displaced 3H-5-HT from its specific binding site (Ki = 0.23 microM) whereas it did not affect 5-HT-sensitive adenylate cyclase. In conclusion, it is likely that the high affinity binding site for 3H-5-HT and the 5-HT-sensitive adenylate cyclase belong to two different postsynaptic 5-HT receptors in the rat brain.

Adenylyl Cyclases↗
PubMed1979

Symmetric bilateral changes in dopamine release from the caudate nuclei of the cat induced by unilateral nigral application of glycine and GABA-related compounds.

The release of [3H]DA synthesized from [3H]tyrosine was estimated in the two caudate nuclei (CN) during the unilateral nigral application of glycine and GABA-related compounds in 'encéphale isolé' cats using push-pull cannulae. Glycine (10(-5) M) reduced the release of [3H]DA in both CN and these effects were antagonized by strychnine (10(-5) M). A decrease in [3H]DA release was also seen in both CN during the unilateral nigral application of diazepam (10(-5) M). In contrast, muscimol (10(-6) M) and GABA (10(-5) M) stimulated [3H]DA release on both sides. The effect of GABA was blocked by picrotoxin (10(-5) M). Picrotoxin alone stimulated the release of [3H]DA in the ipsilateral CN and was without effect in the contralateral side. Bicuculline (10(-5) M) stimulated [3H]DA release only in the contralateral CN. A symmetric increase in [3H]DA release in both CN was also observed during the unilateral nigral application of potassium (30 mM). A model involving a facilitatory polysynaptic pathway originating from the substantia nigra (SN) and acting presynaptically on ther terminals of the contralateral DA neurons is proposed to explain the changes in [3H]DA release induced in the contralateral CN in these various situations. The results are discussed taking into account previous data on the reciprocal control of the two dopaminergic pathways induced by the unilateral nigral application of dopaminergic drugs.

Animals↗
PubMed1979

Effects of the unilateral nigral application of baclofen on dopamine release in the two caudate nuclei of the cat.

"Encéphale isolé" cats were implanted with three push-pull cannulae. The two caudate nuclei (CN) were superfused continuously with 3H-tyrosine to measure the release of 3H-DA in serially collected fractions. Three hours after the beginning of the experiment, d,l-baclofen, d- or l-baclofen or gamma-hydroxybaclofen were introduced for 15 min in the medium used to superfuse the left substantia nigra. d,l-Baclofen (10(-6) M) stimulated 3H-DA release in the ipsilateral as well as in the contralateral CN but the effect was more pronounced in the ipsilateral CN. Similar effects were observed with l-baclofen. d-Baclofen and gamma-hydroxybaclofen were inactive. The results obtained are discussed in the light of effects previously observed during the nigral application of gamma-aminobutyric acid (GABA) and related compounds.

Animals↗
PubMed1979

Effect of nerve activity on the in vivo release of [3H]serotonin continuously formed from L-[3H]tryptophan in the caudate nucleus of the cat.

A new isotopic approach has been developed to study the in vivo release of serotonin (5-HT). 'Encéphale isolé' cats were implanted with a push-pull cannula in the ventrocaudal part of the head of the caudate nucleus to estimate the release of [3H]5-HT continuously synthesized from L-[3H]tryptophan. Both [3H]5-HT and [3H]tryptamine were found in superfusates. Resting steady state in the release of [3H]indoleamines was observed as soon as 20 min after the beginning of the superfusion with L-[3H]tryptophan; the levels of [3H]5-HT in superfusates were 2.5 times those of [3H]tryptamine and about 6 times the blank value. They were markedly enhanced in the presence of fluoxetine (5 x 10(-6)M), a blocker of the 5-HT uptake process. A marked increase in the release of [3H]5-HT was seen during the local depolarization of 5-HT terminals with potassium chloride (60 mM) or batrachotoxin (10(-6)M) or during the stimulation of 5-HT cell bodies in the nucleus raphe dorsalis with L-glutamic acid (5 x 10(-5)M). These treatments did not enhance the efflux of [3H]tryptamine. The potassium-evoked release of [3H]5-HT was reduced by LSD (10(-5)M). LSD added alone in the superfusing fluid was without effect. The batrachotoxin-evoked release of [3H]5-HT was inhibited in the presence of tetrodotoxin (9 x 10(-6)M). The spontaneous release of [3H]5-HT and [3H]tryptamine was markedly reduced in the presence of a calcium-free medium containing cobalt (10 mM). A transient slight reduction in the spontaneous release of [3H]5-HT was observed in the presence of tetrodotoxin (9 x 10(-6)M). The local cooling of 5-HT cell bodies with a cryoelectrode induced a slight reversible decrease in [3H]5-HT release. These last two treatments were without significant effect on [3H]tryptamine efflux in superfusates. These results indicate that the release of [3H]5-HT endogenously formed from [3H]tryptophan is dependent on nerve activity and that this is not the case for [3H]tryptamine. The advantages of the isotopic approach for in vivo studies on the release of 5-HT are discussed.

Animals↗
PubMed1979

Blockade by benzodiazepines of the selective high increase in dopamine turnover induced by stress in mesocortical dopaminergic neurons of the rat.

The effects of electrical foot shock on the activity of the ascending dopaminergic neurons were estimated in the rat by measuring the changes in DOPAC and DA levels in discrete brain areas. DOPAC and DA levels were estimated with a radioenzymatic method in microdiscs of tissues punched out from serial frontal sections of the brain. A marked rise in the ratio of DOPAC/DA levels resulting from an increase of DOPAC and a decrease of DA levels was found in the cerebral frontal cortex at the end of a 20 min stress. The effect was less pronounced in stress of shorter duration from 3 to 10 min and was only related to a reduction of DA levels. Using the DOPAC/DA ratio as an index of the activity of the neurons, the mesocortical dopaminergic neurons were found to be selectively activated under stress since this ratio was increased in the frontal and cingular cortices but not in limbic structures such as the septum, the amygdala and the nucleus accumbens or in the striatum. Finally, pretreatment of the rats with diazepam (5 mg/kg i.p.) or chlordiazepoxide (10 mg/kg i.p.) prevented the increase in the DOPAC/DA ratio in the frontal cerebral cortex of rats submitted to the 20 min stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Effects of the unilateral nigral application of dopaminergic drugs on the in vivo release of dopamine in the two caudate nuclei of the cat.

The effects of the unilateral application of d-amphetamine, benztropine, haloperidol and thioproperazine to one substantia nigra on the release of 3H-dopamine (3H-DA) in the two caudate nuclei were examined in halothane-anesthetized cats. For this purpose animals were implanted with push-pull cannulae and 3H-DA was estimated in superfusates during the continuous delivery of L-3,5-3H-tyrosine. The nigral application of d-amphetamine (10-6 M) or benztropine (10-6 M) reduced the release of 3-H-DA in in the ipsilateral caudate nucleus and induced an opposite effect in the contralateral side. In contrast, the nigral application of haloperidol (10-6 M) or thioproperazine (10-6 M) slightly increased the release of 3H-DA in the ipsilateral caudate nucleus and induced a reduction of 3H-transmitter release in the contralateral side. These results emphasize the role of the dendritic release of DA in the control of the activity of dopaminergic neurons and confirm our previous findings concerning the existence of a reciprocal control in the activity of the two dopaminergic pathways.

Animals↗
PubMed1979

In vitro and in vivo disposition of 3H-methiothepin in brain tissues. Relationship to the effects of acute treatment with methiothepin on central serotoninergic receptors.

A single treatment with a large dose of methiothepin (20 mg/kg, i.p.) induced, as early as the 2nd day after injection, a significant increase (+20--35%) in the number of specific binding sites for 3H-5-HT in forebrain areas, particularly the hippocampus. Experiments with 3H-methiothepin indicated that the drug remained firmly bound to brain membranes thus maintaining a local concentration high enough to effectively block 5-HT receptors for 10--12 h after its peripheral administration. Accordingly, it can be concluded that the occupancy of central 5-HT receptor sites by methiothepin for several hours was sufficient to induce a supersensitivity phenomenon within the two following days. Although 3H-methiothepin was a useful marker for analyzing the disposition and the kinetics of the 5-HT antagonist in brain tissues, it could not be used as a specific ligand of 5-HT receptors in brain since under in vitro as well as in vivo conditions most of 3H-methiothepin bound to non-specific sites, especially to the lipid component of the membranes.

Adenylyl Cyclases↗