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Biomedical subjects

J Glowinski

Publications and source records attributed to J Glowinski.

At least 451 records · Page 25Linked to original sources
PubMed1977

Effects of peripheral and local administration of picrotoxin on the release of newly synthesized 3H-dopamine in the caudate nucleus of the cat.

The release of 3H-DA was estimated in superfusates of a superfusion cannula introduced into the caudate nucleus of "encéphale isolé" cats. 3H-DA was continuously formed from L-3,5-3H-tyrosine introduced into the superfusion medium. Injected at the periphery, picrotoxin (2.5 mg/kg, i.p.) markedly enhanced the release of 3H-DA, the effect being particularly pronounced 90 min after the drug injection. The effects of the local introduction of picrotoxin into the substantia nigra and into the caudate nucleus on 3H-DA release were also examined to ensure the specificity of the result. Picrotoxin (10(5) M) added into the superfusing medium of a second superfusion cannula introduced in to the substantia nigra enhanced by 2 to 5 times the release of 3H-DA during the drug application. No effect could be seen when the tip of the superfusion cannula was not exactly localized into the substantia nigra. Although less pronounced, a stimulation of 3H-DA release was also seen when picrotoxin(10(6) M) was added directly into the superfusion medium of the cannula introduced into the caudate nucleus. These results suggest that some gabaergic neurons are involved in the control of DA release by acting on dopaminergic cell bodies or dendrites into the substantia nigra. Other gabaergic neurons may directly or indirectly act on dopaminergic terminals within the caudate nucleus.

Animals↗
PubMed1977

The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat.

The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat was established owing to the combined use of microdissection techniques and biochemical microassays. The density of 5-HT terminals in various areas of both structures was quantified first by measuring 5-HT levels in microdiscs of frozen tissue. Since the high affinity uptake process for 5-HT appeared undamaged in isotonic homogenates of previously frozen (--5 degrees C) tissues, it was possible to confirm the findings obtained with the measurement of 5-HT levels by also determining 5-HT uptake activity in these microdiscs. However, in the rat neostriatum, but not in the cat caudate nucleus, [3H]5-HT even at a very low extracellular concentration (4.4 -x 10(-8) M) was taken up not only by serotoninergic terminals but also to a significant extent by dopaminergic terminals. In presence of benztropine, this second component was suppressed and [3H]5-HT uptake activity could then be considered as a specific marker of serotoninergic terminals also in the neostriatum of the rat. In both species, 5-HT terminals were mainly localized in the ventrocaudal area of the structure. In this area, 5-HT levels were among the highest values found in the brain (17 ng/mg protein). The density of 5-HT terminals decreased progressively from the acudal to the rostral planes of the neostriatum in rats or the caudate nucleus in cats. The poorest area, i.e. the dorsorostral zone, contained about 4 times less 5-HT than the ventrocaudal zone of the structure. Electrolytic lesion of the dorsalis (B7) and centralis superior (B8) raphe nuclei during early life resulted in a large decrease of 5-HT levels (--90%) in various parts of the neostriatum of adult rats. The present findings might be of interest to further analyze the role of serotoninergic neurons in extrapyramidal functions.

Animals↗
PubMed1977

Origin of the acetyl moiety of acetylcholine synthesized in rat striatal synaptosomes.

The subcellular localization of the AcCoA compartment supplying the cytoplasmic choline acetyltransferase (ChAc, EC 2.3.1.6) was investigated using a purified preparation of rat striatal synaptosomes (B fraction). It was first demonstrated that the SRA of the [14C]ACh synthesized during a 10 min incubation period was equal to the SRA of the [2-14C] and the [3-14C]pyruvate added to the isolated nerve terminal suspension. The experimental results can be summarised as follows: (i) No modification in the amount of [14C]ACh synthesized from [2-14C]pyruvatetion in the amount of [14C]ACh synthesized from [2-13C]pyruvate could be detected after the addition of high concentrations of either carnitine, acetylcarnitine or acetyl phosphate to the synaptosomal suspension. (ii) Under experimental conditions in which the amount of [1,5-14C]citrate taken up by passive diffusion into the cholinergic nerve endings would allow detection of the possible formation of the labelled ester, no [14C]ACh could be recovered. (iii) The SRA's of the individual carbon atoms of the Krebs cycle intermediary compounds when the cycle is fed with [2-14C] and [3-14C]pyruvate were calculated as a function of the STA's of each of these two precursors (a and a' respectively), of the number of 14CO2 dpm produced in the Krebs cycle from each of these two labelled compounds (D2 and D3 respectively), and as the function of the rate y of exchanges of molecules between the tricarboxylic acid cycle and other metabolic compartments. The experimental value obtained from a 10 min incubation, after the nerve endings had reached a steady metabolic activity, indicate that if the acetyl moiety of ACh was derived from some Krebs cycle intermediary compounds, its SRA could never exceed 55 per cent that of the [2-14C]pyruvate from which it is produced, (iv) No correlation could be found between the rate of [14C]ACh formation and changes in the Krebs cycle activity induced by sodium cyanide, 2-4 dinitrophenol and Ca2+ free medium. (v) The lack of significant [14C]ACh synthesis from [1-14C]acetate in striatal synaptosomes is consistent with the failure of fluoroacetate to modify the amounts of 14CO2 as well as of [14C]ACh formed from [2-14C]pyruvate. These results were interpreted as a confirmation of the presence of a low AcCoA synthetase activity in the nerve terminals. To reconcile all these data, it is proposed that pyruvate is transformed into AcCoA outside the mitochondria by the action of some cytoplasmic pyruvate dehydrogenase-like enzyme.

Acetates↗
PubMed1977

Involvement of cholinergic presynaptic receptors of nicotinic and muscarinic types in the control of the spontaneous release of dopamine from striatal dopaminergic terminals in the rat.

Rat striatal slices (two) were superfused continuously with L-3,5-3H tyrosine and 3H-dopamine (3H-DA) release was estimated in serial fractions of superfusates. The spontaneous release of 3H-DA was reduced by about 50% when slices were superfused with a calcium-free medium containing ethylene glycol bis (beta-aminoethyl ether)- N,N'-tetraacetic acid (EGTA) (10(-4) M) or with a medium containg tetrodotoxin (5 x 10(-7) M). These effects were not related to a change in 3H-DA synthesis since the rate of L-3,5-3H tyrosine hydroxylation, as measured by 3H-H2O formation was not significantly reduced. Acetylcholine (ACh) (10(-5) M) stimulated the release of 3H-DA (about 100%). This effect was abolished in the absence of calcium; it was partially blocked by pempidine (10(-5) M), atropine (10(-6) M) or scopolamine (10(-5), 10(-6) M). Oxotremorine (10(-5) M) enhanced 3H-DA release but to a lesser extent (60%) than ACh (10(-5) M); its action was completely blocked by atropine (10(-6) M) and unaffected by pempidine (10(-5) M). The ACh- (10(-5) M) and oxotremorine- (10(-5) M) stimulatine effects on 3H-DA spontaneous release were still detected in slices superfused in the presence of tetrodotoxin (5 x 10(-7) M). In the presence of the neurotoxin, the effect of ACh (10(-5) M) was significantly reduced by pempidine (10(-5) M) and the effect of oxotremorine (10(-5) M) was blocked by atropine (10(-6) M). These results suggest the presence of cholinergic presynaptic receptors of the nicotinic and muscarinic types on striatal dopaminergic terminals.

Acetylcholine↗
PubMed1976

Radioautographic study of in vivo incorporation of 3H-monoamines in the cat caudate nucleus: identification of serotoninergic fibers.

The localization of radioactivity was examined in the caudate nucleus of the cat, treated with an MAO inhibitor, following local superfusion of the ventricular surface of the structure with low concentration of 3H-catecholamines or [3H]5-HT. The caudate nucleus was superfused continuously from 30 to 240 min using a cup technique. Light microscope or high resolution radioautographs revealed: (1) a rather diffuse incorporation of 3H-catecholamines under the subependymal region which could be hardly attributed to a specific population of nerve terminals. A loose binding of 3H-catecholamines into dopaminergic terminals could be involved in this effect. (2) An intense and selective uptake of [3H]5-HT in fine scarce varicose nerve fibers localized in the ventricle as in the subependymal layer and in the neuropil of the nucleus. The labeled fibers contained numerous round or elongated large granular vesicles of 80-120 nm and exhibited only very few synaptic contacts suggesting a possible extrasynaptic liberation of 5-HT.

Animals↗