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Biomedical subjects

F Artaud

Publications and source records attributed to F Artaud.

At least 37 records · Page 2Linked to original sources
PubMed1984

Basic and regulatory mechanisms of in vitro release of Met-enkephalin from the dorsal zone of the rat spinal cord.

Under control conditions, superfused slices of the dorsal half of the lumbar enlargement from adult rats released Met-enkephalin-like material (MELM) that behaved as authentic Met-enkephalin under two different chromatographic procedures (Bio-gel filtration, HPLC). MELM release increased markedly on exposure of slices to batrachotoxin (0.5 microM) or to an excess of K+ (28 and 56 mM instead of 5.6 mM). The K+-evoked release was totally dependent on the presence of Ca2+ in the superfusing fluid whereas the spontaneous efflux of MELM was only partially Ca2+-dependent. Further experiments performed with tissues of polyarthritic rats indicated that the increase in their MELM levels was associated with a lower fractional rate constant of MELM release, therefore suggesting that spinal Met-enkephalin turnover might be reduced in chronically suffering animals. Examination of the possible modulation of MELM release by various neuroactive compounds present within the dorsal horn revealed that cholecystokinin (10 microM), but not its desulphated derivative, substance P-sulphoxide (10 microM), and to a lesser extent substance P, enhanced the K+-evoked MELM release. In contrast, gamma-aminobutyric acid (10 microM) and (-)-baclofen (1 microM) partially prevented the stimulatory effect of K+ on MELM release. Other compounds such as serotonin, somatostatin, and neurotensin altered neither the spontaneous nor the K+-evoked release of MELM.

Animals↗
PubMed1982

In vivo modulations by GABA-related drugs of met-enkephalin release in basal ganglia of the cat brain.

The influence of the intrapallidal application of GABA-related compounds on the release of Met-enkephalin in the globus pallidus and the caudate nucleus in the two hemispheres was investigated in vivo in the cat. For this purpose, the 4 structures were continuously superfused with an artificial CSF through implanted push-pull cannulae and Met-enkephalin released in superfusates was determined using a specific radioimmunoassay. GABA (10-500 microM) reduced the local release of Met-enkephalin during its application but once the amino acid was removed from the superfusing fluid, an increase in the peptide release was observed. Diazepam (10 microM) induced only an inhibitory effect whereas muscimol (1 microM) stimulated Met-enkephalin release. Opposite changes in Met-enkephalin release were also seen with the GABA antagonists, bicuculline methiodide (1 microM) and picrotoxin (10 microM), suggesting that the local regulation of Met-enkephalin release by GABA related compounds may be mediated by at least two types of GABA receptors. In several cases, the unilateral pallidal application of GABA agonists and antagonists induced significant changes in Met-enkephalin release at distant structures. The most striking effect was observed with diazepam which markedly reduced the peptide release in both caudate nuclei and pallida. These data suggest that GABAergic systems can contribute to some bilateral regulation of striato-pallidal enkephalinergic neurones.

Animals↗
PubMed1982

Application of L-glutamic acid and substance P to the substantia nigra modulates in vivo [3H]serotonin release in the basal ganglia of the cat.

L-Glutamic acid or substance P were applied to the caudate nucleus (CN) or substantia nigra (SN) and their effects on local, spontaneous, in vivo [3H]serotonin ([3H]5-HT) release as well as [3H]5-HT release in the contralateral CN and SN were studied using cats implanted with push-pull cannulae. L-Glutamic acid (5 x 10(-5) M), when applied to the CN or SN inhibited the local release of [3H]5-HT but did not affect release in the contralateral CN and SN. In the SN, the L-glutamic acid effect was blocked by L-glutamic acid diethylester. Substance P (10(-7) M) applied to the SN induced an increase in [3H]5-HT release that was delayed in onset. Furthermore, [3H]5-HT release was elevated in the contralateral CN immediately upon the application of substance P to the SN. These results suggest that L-glutamic acid and substance P may control 5-HT transmission in the basal ganglia.

Animals↗
PubMed1982

Sensory stimuli differentially affect in vivo nigral and striatal [3H]serotonin release in the cat.

The effect of auditory, visual and peripheral nerve stimulation on in vivo [3H]serotonin release in both caudate nuclei and substantiae nigrae was studied in either awake 'encéphale isolé' or halothane-anesthetized cats. Release of endogenously synthesized [3H]serotonin was estimated in each brain structure, using push--pull cannulae, continuously superfused with [3H]tryptophan. Bilateral and simultaneous application of click noises and light flashes to awake 'encéphale isolé' cats enhanced [3H]serotonin release in both substantiae nigrae but was without effect on striatal [3H]serotonin release. Unilateral, low intensity electrical stimulation of the forepaw of halothane-anesthetized cats diminished [3H]serotonin release in both caudate nuclei and the ipsilateral substantia nigra. No effect was observed in the contralateral substantia nigra. In contrast, high-intensity electrical stimulation of one forepaw increased [3H]serotonin release in the ipsilateral substantia nigra but was without significant effect on release in the other brain areas examined. The results are discussed in light of previously known anatomical data concerning serotoninergic pathways and electrophysiological evidence of the effect of sensory stimuli on serotoninergic neurons. Our findings suggest that serotonin neurons may serve an important function in the integration of sensory information.

Acoustic Stimulation↗
PubMed1982

Involvement of lateral habenula-dorsal raphe neurons in the differential regulation of striatal and nigral serotonergic transmission cats.

The importance of the lateral habenula-dorsal raphe pathway in the control of in vivo [3H]serotonin release in the cat basal ganglia was examined using the push-pull cannula technique and an isotopic method for the estimation of [3H]serotonin continuously formed from [3H]tryptophan. [3H]Serotonin was measured in both caudate nuclei and substantiae nigra and, in some cases, in the dorsal raphe. Electrical stimulation of the lateral habenula decreased [3H]serotonin release in all structures studied. Blockade of the GABA inhibitory pathway to the lateral habenula by the local application of picrotoxin reduced [3H]serotonin release in both substantiae nigra and increased release of the 3H-amine in the dorsal raphe but was without effect on [3H]serotonin release in either caudate nucleus. This inhibition of nigral [3H]serotonin release was antagonized by simultaneous application of picrotoxin to the dorsal raphe. Substance P delivery to the dorsal raphe produced the same effects on [3H]serotonin release as described for picrotoxin application to the lateral habenula except that inhibition of nigral [3H]serotonin release was not prevented by local co-administration of picrotoxin. These results suggest that the lateral habenula can control serotonergic transmission in the basal ganglia and that this regulation may be different for those serotonergic neurons innervating the caudate nucleus versus those projecting to the substantia nigra.

Animals↗
PubMed1981

In vivo evidence for GABAergic control of serotonin release in the cat substantia nigra.

Push-pull cannulae were used for estimating the release of endogenously synthesized [3H]serotonin in both substantia nigra and caudate nuclei of halothane-anaesthetized cats. The unilateral nigral application of GABA (10-5 M) reduced the local release of [3H]serotonin picrotoxin induced an opposite effect. Both treatments failed to modify [3H]serotonin release in the caudate nuclei or in the contralateral substantia nigra. These results suggest that GABAergic neurons innervating the substantia nigra may regulate nigral serotonin transmission. The possibility that such a regulation could be presynaptic (direct or through other nigral neurotransmitters) or related to a change in the activity of the nigro-raphe projection is discussed.

Animals↗
PubMed1981

The respective roles of tryptophan uptake and tryptophan hydroxylase in the regulation of serotonin synthesis in the central nervous system.

1. The rate limiting enzyme for the synthesis of serotonin (5-HT) in brain, tryptophan hydroxylase, is not saturated under normal physiological conditions. 2. Therefore, any decrease or increase in brain tryptophan levels results in a reduction or a stimulation of 5-HT synthesis respectively. Thus, mechanisms controlling brain tryptophan levels, i.e. the concentration of free tryptophan in serum and the intrinsic activity of the tryptophan carrier in neuronal membranes, exert in fact a tonic regulation of 5-HT synthesis in central serotoninergic neurons. 3. Changes in the rate of 5-HT synthesis can also involve modifications in the intrinsic activity of tryptophan hydroxylase. This occurs in vivo following the intrastriatal injection of kainic acid and in vitro during the depolarization of brain slices. In both cases, an activation of tryptophan hydroxylase due to an increase in its apparent Vmax is detected in soluble extracts. 4. The depolarization-induced activation of tryptophan hydroxylase in brain slices very likely involves a Ca2+-dependent phosphorylation process. 5. Rapid changes in tryptophan hydroxylase activity produced by a phosphorylation-dephosphorylation process may be involved in the phasic regulation of 5-HT synthesis in serotoninergic neurons.

Animals↗
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

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↗
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↗
PubMed1978

Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker.

Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3-H-5-HT onto synaptosomal membranes (IC 50 = 18 nM) and the stimulating effect of 10 micron 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50 = 12 micron. In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3-H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2-10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.

Adenylyl Cyclases↗