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S Bourgoin

Publications and source records attributed to S Bourgoin.

At least 109 records · Page 6Linked to original sources
PubMed1987

Chronic chlorimipramine does not reverse the reduction of cerebrospinal fluid Met-enkephalin-like immunoreactivity in chronic-pain patients.

Chronic-pain patients were treated for 10 days with chlorimipramine (100 mg i.v. daily), and their plasma levels of the drug and cerebrospinal fluid (CSF) levels of Met-enkephalin-like material (MELM) were measured for a comparison with those found in untreated chronic-pain patients and in control subjects. Pain relief in chlorimipramine-treated patients was apparently not associated with pronounced changes in the activity of enkephalinergic systems since the mean CSF levels of MELM were reduced to the same extent in treated (-49%) and untreated (-45%) pain patients as compared with controls. However, subtle chlorimipramine-induced alterations likely occurred as revealed by the simultaneous measurement of the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA) in the same patients. Indeed, a positive correlation (r = 0.667) was found between CSF 5-HIAA and MELM levels in control subjects, whereas a negative correlation (r = 0.691) between these two parameters was detected in chlorimipramine-treated patients. These data suggest that chlorimipramine alters probable functional serotonin-enkephalin interactions in pain patients.

Adult↗
PubMed1987

Enkephalinase is involved in the degradation of endogenous substance P released from slices of rat substantia nigra.

The effects of various peptidase inhibitors were examined upon the K+-evoked overflow of substance-like immunoreactive material (SPLI) from slices of rat substantia nigra in order to assess the possible involvement of "enkephalinase," angiotensin-converting enzyme (ACE) and calpain in the enzymatic inactivation of endogenous substance P in brain tissues. The calpain inhibitor leupeptin and the enkephalinase inhibitors thiorphan and phosphoramidon increased markedly SPLI overflow, whereas the two ACE inhibitors, captopril and enalaprilat (up to 10 microM in the superfusing medium), were inactive. Surprisingly kelatorphan, which inhibits not only enkephalinase but also aminopeptidase and dipeptidylaminopeptidase activities, was less potent than thiorphan or phosphoramidon to enhance SPLI overflow. However, in the presence of ICI-154129 or naloxone to block opiate receptors, kelatorphan was as potent as thiorphan, therefore suggesting some negative influence of endogenous opioids on SPLI release with kelatorphan but not thiorphan. In agreement with this interpretation, the direct stimulation of delta opiate receptors by deltakephalin was found to significantly reduce SPLI overflow. Furthermore, an increased outflow of [Met]enkephalin-like material was observed from substantia nigra slices superfused with kelatorphan but not thiorphan. These results indicate that endogenous substance P released within the substantia nigra is very probably inactivated by enkephalinase and calpain, but not ACE. They also demonstrate that endogenous opioids can exert a negative control upon substance P release in this brain region.

Animals↗
PubMed1987

[SIN-1 interactions with the generation of cyclic nucleotides and arachidonate oxide metabolites in the uterine muscle].

In the uterine smooth muscle, SIN-1 stimulated cGMP accumulation independently of the presence of Ca2+ and activated the soluble form of guanylate-cyclase through mechanisms apparently similar to those involved in the stimulations evoked by NO-containing compounds. These activations appear different from those induced by hydroperoxy-unsaturated fatty acids and which contribute to the carbachol-mediated cGMP accumulation. SIN-1 did not influence the rise in cAMP of the biosynthesis of PG1(2) and 12-HETE due to exogenous arachidonic acid. By contrast, SIN-1 markedly inhibited the increased synthesis of PG1(2) induced by the ionophore A23187 which was due to a prior, Ca2+-dependent, liberation of endogenous arachidonic acid. The data suggests an interference of SIN-1 with the generation and/or the expression of the Ca2+ signal.

Animals↗
PubMed1987

[Effect of SIN-1 on the synthesis of leukotrienes in human polymorphonuclear cells].

Leukotriene (LT) synthesis triggered with ionophore A23187 or inflammatory stimuli (PAF, fMLP) in human polymorphonuclear leukocytes (PMNL) was markedly decreased by SIN-1, an active metabolite of molsidomine. This inhibition occurred in the absence or in the presence of exogenous arachidonic acid (AA). These results suggest that SIN-1 inhibited both the release of AA from membrane phospholipids and the 5-lipoxygenase activity in human PMNL. Molsidomine was without any effect on LT formation.

Arachidonic Acids↗
PubMed1986

Distribution of Met-enkephalin immunoreactive fibres in the thalamus of the cat.

The Met-enkephalin-like immunoreactivity was studied in the thalamus of the cat using an indirect immunoperoxidase method. The densest network of immunoreactive fibres and terminals was observed in the epithalamus and the intralaminar nuclei, particularly those located along the midline nuclei interanteromedialis, submedius, rhomboidens and reuniens. The nuclei parafascicularis and centrum medianum contained also numerous immunoreactive fibres and terminals, whereas the lamina medullaris externa had a lower density of immunoreactive terminals. Enkephalin fibres were almost totally absent in the lateral nuclei of the thalamus, and in the posterior group only the magnocellular part of the corpus geniculatum mediale contained some immunoreactive fibres.

Animals↗
PubMed1986

Effects of kelatorphan and other peptidase inhibitors on the in vitro and in vivo release of methionine-enkephalin-like material from the rat spinal cord.

The effects of the novel mixed peptidase inhibitor, kelatorphan [N-(R)-3-(N-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)-L-alanine], were compared to those of a combination of the potent "enkephalinase" inhibitor thiorphan and the nonselective aminopeptidase inhibitor bestatin, on the catabolism of [3H]Met-enkephalin and on the release of endogenous Met-enkephalin by the rat spinal cord in vitro and in vivo. At 20 microM, kelatorphan almost prevented completely the degradation of exogenous [3H] Met-enkephalin by slices of the dorsal zone of the lumbar enlargement. Similarly, the addition of 20 microM kelatorphan to a [3H] Met-enkephalin-containing artificial cerebrospinal fluid superfusing the whole spinal cord of halothane-anesthetized rats efficiently protected the exogenous peptide from enzymatic degradation. In contrast, in the same in vitro and in vivo models, thiorphan (1 microM) or bestatin (20 microM) alone was inactive, and only their combination induced a significant protection of the exogenous peptide. In vitro and in vivo, kelatorphan (20 microM) increased markedly the spontaneous outflow of endogenous Met-enkephalin-like material as well as the peptide overflow due to K+-induced depolarization (in vitro and in vivo) or noxious stimulation (in vivo). Under similar conditions, thiorphan (1 microM) plus bestatin (20 microM) also enhanced the efflux of Met-enkephalin-like material, but generally to a lower extent than kelatorphan. Compared to thiorphan plus bestatin, kelatorphan exerts additional inhibitory effects on dipeptidylaminopeptidase activity and the present results could indicate that this enzyme also may be involved in the inactivation of extracellular Met-enkephalin at the spinal level in rats.

Animals↗
PubMed1985

Local and remote effects of intra-caudate administration of GABA-related drugs on Met-enkephalin release in the basal ganglia.

The possible influence of GABAergic systems on the activity of enkephalinergic neurones within the basal ganglia was examined by measuring the release of Met-enkephalin in the caudate nuclei and pallida of halothane-anesthesized cats treated by intra-caudate applications of GABA-related drugs. Depending on the concentration used, GABA exerted local stimulatory (at 10 microM of the amino acid) or inhibitory (at 0.5 mM) action on Met-enkephalin release in the cat caudate nucleus. Only the inhibition was reproduced by the GABA agonists muscimol (1 microM) and (-)-balcofen(10 microM) and by diazepam 10 microM). Conversely, the intra-caudate application of the GABA antagonist bicuculline enhanced markedly the local release of the pentapeptide. Complementary studies using slices of the rat striatum (caudate nucleus + putamen) revealed that a low concentration of GABA (10 microM) tended to increase the K+-evoked efflux of Met-enkephalin, whereas a high concentration of the amino acid exerted a strong inhibitory effect on the peptide release. Such in vivo and in vitro findings suggest that the GABA-induced inhibition of Met-enkephalin release took place via the stimulation of specific GABA A and GABA B receptors within the caudate nucleus, whereas the GABA-induced increase of the peptide release might involve some intracellular regulatory processes in striatal neurones containing both GABA and enkephalins. In addition to altering the local release of Met-enkephalin, intra-caudate applications of GABA-related drugs affected the peptide release in the ipsilateral globus pallidus and contralateral basal ganglia. The observed changes suggest that GABA A, but not GABA B, receptors participated in some tonic inhibitory influence of striatal GABAergic neurones on the striato-pallidal enkephalinergic system. Furthermore, the present results confirmed previous studies (Bourgoin et al.) showing that GABAergic neurones can contribute to some bilateral modulation of enkephalinergic neurones within the basal ganglia.

Animals↗
PubMed1985

In vitro and in vivo effects of kelatorphan on enkephalin metabolism in rodent brain.

Biologically relevant assays were used to compare the potency of kelatorphan (N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine) as inhibitor of the peptidase-induced metabolism of enkephalins to that of bestatin, a non-specific inhibitor of aminopeptidase and thiorphan, a highly potent blocker of the neutral endopeptidase (EC 3.4.24.11) designated as enkephalinase. Kelatorphan almost completely inhibited the formation of the three metabolites [3H]Tyr, [3H]Tyr-Gly and [3H]Tyr-Gly-Gly produced by incubation of [3H][Tyr1,Met5]enkephalin with rat striatal slices. Co-administered with [Met5]enkephalin in mouse brain, kelatorphan was able to prevent by 80% the degradation of the exogenous peptide. Moreover, a mixture of thiorphan (1 microM) and bestatin (20 microM) or kelatorphan alone (20 microM) induced a 2.2 to 2.5-fold increase in endogenous [Met5]enkephalin overflow after evoked depolarization of superfused rat striatal slices. In this assay, kelatorphan was the only compound to increase by 63% the basal level of released [Met5]enkephalin. Kelatorphan was about 100 times less potent than bestatin to inhibit the total rat striatal aminopeptidases, but as efficient (IC50 = 4 X 10(-7) M) as bestatin to inhibit a minor aminopeptidase activity resembling aminopeptidase M. Therefore the reported enhanced analgesic potency of kelatorphan with regard to the association of bestatin and thiorphan is very likely related to its ability to almost completely inhibit enkephalin-degrading enzymes (including the Tyr-Gly releasing peptidase) and to its better selectivity for the biologically relevant aminopeptidase M. Kelatorphan would be a valuable probe, preferable to the association of bestatin and thiorphan, to investigate the physiological functions regulated by a phasic enkephalinergic activity.

Aminopeptidases↗
PubMed1985

Spontaneous and evoked release of methionine-enkephalin-like material from the rat spinal cord in vivo.

In vivo perfusion of the subarachnoid space with an artificial cerebrospinal fluid (CSF) in paralyzed halothane-anesthetized rats allowed the collection of methionine-enkephalin (Met-Enk)-like material (MELM) released from the spinal cord. Bio-Gel P2 chromatography and high-performance liquid chromatography showed that 65% of this material corresponded to authentic Met-Enk. Under resting conditions, about 1 pg of MELM per minute was regularly released for at least 3 h; for Met-Enk, this value corresponded to a fractional rate constant of 0.002% (i.e. tissue content of the pentapeptide which was released per minute from the whole spinal cord). Perfusion with K+-enriched (40-60 mM) CSF resulted in a marked enhancement (+ 150-200%) of spinal MELM release. Similarly, calibrated pinches of the muzzle and i.p. administration of acetic acid, two strong noxious stimuli in awake animals, induced a significant increase (+ 75-150%) in spinal MELM release. In contrast, pinches applied to the tail did not enhance but instead slightly reduced (-35%) MELM release from the rat spinal cord. These data suggest that mechanisms other than segmental controls could be involved in the activation of spinal enkephalinergic neurons by some nociceptive stimuli.

Animals↗
PubMed1985

[The spinal enkephalinergic and serotoninergic systems in the control of transmission of nociceptive messages].

Numerous anatomical, pharmacological and electrophysiological data described in the literature indicate that spinal enkephalinergic and serotoninergic systems are probably involved in the control of nociceptive inputs from the periphery to the cerebral cortex. However, reported evidence was generally indirect and did not provide a real demonstration of the physiological participation of these neurones in pain control. This led us to select appropriate experimental approaches for studying directly the activity of spinal enkephalinergic and serotoninergic systems in animals (rat, cat) submitted to noxious stimuli. Owing to two catheters introduced into the subarachnoidal space of anesthetized rats, it was possible to perfuse the whole spinal cord with an artificial cerebro-spinal fluid and thus collect the neuroactive compounds released by spinal neurones (at least those in superficial layers) under various experimental conditions. Using this technique, we observed that some (but not all) nociceptive stimuli such as intense pinching of the muzzle, intraperitoneal injection of acetic acid or noxious heat applied to the muzzle or the tail induced a significant increase in met-enkephalin release from the spinal cord (see fig. 2). Similar effects were observed following the blockade of enkephalin catabolism by thiorphan and bestatin (see fig. 1) indicating that they were not due to some alteration of peptidase activities but really involved the activation of spinal enkephalinergic systems. Since cervical cord transection suppressed the stimulatory action of noxious stimuli on spinal met-enkephalin release, it could be proposed that the mechanisms involved were not limited to the cord but depended on supraspinal structures. Bulbo-mesencephalic serotoninergic neurones projecting to the spinal cord might well correspond to such structures (or at least to some of them) since nociceptive stimuli (such as noxious heat applied to the tail) also evoked a marked increase of serotonin (5-HT) release at the spinal level (fig. 3). Such observations together with indirect evidence reported in the literature suggested therefore that the activation of spinal enkephalinergic systems triggered by noxious stimuli might result from excitatory influence due to descending serotoninergic projections. However, in vitro studies using slices of the dorsal zone of the rat lumbar cord did not reveal any stimulatory effect of 5-HT on the spontaneous or K+-evoked release of met-enkephalin (fig. 4).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain.

In vitro investigations revealed that PAT (8-hydroxy-2-(n-dipropylamino)tetralin) interacted with postsynaptic 5-HT receptors in the rat brain: the drug stimulated 5-HT-sensitive adenylate cyclase in homogenates of colliculi from new-born rats (KAapp 8.6 microM) and inhibited the specific binding of [3H]5-HT to 5-HT1 sites. The PAT-induced inhibition of [3H]5-HT binding showed marked regional differences compatible with a preferential interaction of PAT (IC50 2 nM) with the 5-HT1A subclass. As previously seen with 5-HT agonists, the efficacy of PAT for displacing [3H]5-HT bound to hippocampal membranes was markedly increased by Mn2+ (1 mM) and reduced by GTP (0.1 mM). PAT also affected presynaptic 5-HT metabolism since it inhibited competitively (Ki 1.4 microM) [3H]5-HT uptake into cortical synaptosomes and reduced (in the presence of the 5-HT uptake inhibitor fluoxetine) the K+-evoked release of [3H]5-HT previously taken up or newly synthesized from [3H]tryptophan in cortical or striatal slices. This latter effect was prevented by 5-HT antagonists (methiothepin, metergoline) suggesting that it was mediated by the stimulation of presynaptic 5-HT autoreceptors by PAT. Like 5-HT, PAT counteracted the stimulatory effect of K+-induced depolarization on the synthesis of [3H]5-HT from [3H]tryptophan in cortical slices. It is concluded that PAT is a potent 5-HT agonist acting on both post- and presynaptic 5-HT receptors in the rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1984

Normal CSF levels of met-enkephalin-like material in a case of naloxone-reversible congenital insensitivity to pain.

In a case of naloxone-reversible congenital insensitivity to pain, met-enkephalin-like immunoreactivity in the CSF was in the normal range and not affected by the administration of naloxone. Chromatographic analysis of the met-enkephalin-like material revealed that it corresponded to at least two classes of molecules. A clear difference in the relative proportions of these two classes was detected in the CSF of the patient insensitive to pain when compared to controls. The possible functional significance of this alteration is discussed in relation to the well known antinociceptive action of enkephalins.

Adult↗
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↗
PubMed1983

Different localizations of Met-enkephalin-like immunoreactivity in rat forebrain and spinal cord using hydrogen peroxide and Triton X-100. Light microscopic study.

The histological distribution of met-enkephalin-like immunoreactivity was studied in the forebrain (particularly the striatum) and the spinal cord of the rat using the indirect peroxidase-labelled antibody method. In most experiments, vibratome sections of formaldehyde-fixed tissues and purified antibodies were used. The search for optimal conditions for the immunohistochemical reaction lead us to establish that met-enkephalin-containing perikarya of both untreated and colchicinized animals were better demonstrated when tissue were pre-treated with diluted hydrogen peroxide only. The additional treatment of these sections with Triton X-100 (or some other detergents) resulted in the near disappearance of the perikaryal immunoreactivity; on the contrary, numerous met-enkephalin containing nerve fibres and varicosities were then demonstrated in the same region. Using only the hydrogen peroxide treatment, we found numerous met-enkephalin-containing perikarya in the medial and ventral regions of the neostriatum. This distribution was prolonged caudally by the existence of a prominent group of stained somata in the ventral putamen-central nucleus of the amygdala. When intraventricular injections of colchicine were used, positive perikarya were more numerous within the striatum (the globus pallidus excepted) but their distribution was largely the same as in non injected animals. However, some new groups of somata were stained in this case in the forebrain (in the lateral septum, the olfactory tubercle and the hypothalamus particularly). In control animals only few met-enkephalin-containing perikarya were observed in the dorsal horn of the spinal cord when H2O2 pretreatment was used alone and they were numerous only when intraspinal injections of colchicine were performed. Met-enkephalin-containing fibres and varicosities, which were scattered in the whole neostriatum in the conditions used above, became very numerous when the tissue sections were incubated in the presence of Triton X-100. Their density increased markedly from the latero-dorsal to the medio-ventral regions but, in addition, an organization under the form of islands of stronger immunoreactivity was also evidenced. These islands were more numerous ventrally in the anterior neostriatum and in the central region of the "putamen." The dense plexus of immunoreactive nerve fibers forming "tube-like structures" which was always observed in the paleostriatum and in the cranial medial forebrain bundle (islands of Calleja) appeared more diffuse when detergents were used.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Met-enkephalin-like immunoreactivity in rat forebrain and spinal cord using hydrogen peroxide and Triton X-100. Ultrastructural study.

Using two immunocytochemical methods, we have shown in light microscopy that the met-enkephalin-like immunoreactivity within striatum and spinal cord of the rat is differentially distributed in either perikarya or nerve terminals according to the technical conditions used [1]. The present electron microscopic study has been undertaken in order to elucidate the subcellular localization of immunoprecipitates according to the same technical conditions. In the neostriatum, numerous met-enkephalin-containing perikarya were stained (principally at the level of rough endoplasmic reticulum) when tissue sections were treated with hydrogen peroxide (H2O2) only, prior to the immunocytochemical procedure. However, injections of colchicine were required to demonstrate perikarya in the dorsal horn of the spinal cord. At variance with previous results, numerous dendritic profiles and nerve terminals were also reactive in this condition. Neurotubules, mitochondria, large granular vesicles (LGVs) and small synaptic vesicles were stained within these structures. The addition of a low concentration of Triton-X-100 (0.02%) in the first incubation medium often resulted in the disappearance of most perikarya and in the staining of only LGVs in nerve terminals. The addition of a higher concentration of Triton-X-100 (0.1%) produced diffusion of immunoprecipitates at the level of nerve terminals, which was probably responsible for the increased intensity of staining and, subsequently, for the better demonstration of fibre varicosities in light microscopy. On the contrary, the disappearance of reactive perikarya seemed to result from the diffusion of the non-protected peptide out of the cytoplasm. The diverse ultrastructural localizations of met-enkephalin-like immunoreactivity in striatum and spinal cord are finally discussed in light of intrinsic connections or afferents described in the literature.

Animals↗
PubMed1983

Localization of Met-enkephalin-like immunoreactivity within pain-related nuclei of cervical spinal cord, brainstem and midbrain in the cat.

Met-enkephalin immunoreactivity was investigated with an indirect immunoperoxidase technique in the cervical spinal cord, brainstem and midbrain of the cat, paying special attention to pain-related nuclei. Different technical conditions were used to reveal preferentially met-enkephalin-containing fibres and terminals or perikarya. Immunoreactive fibres and terminals were revealed optimally in sections from control animals incubated with detergent (Triton X-100). Immunoreactive perikarya were revealed in colchicine treated animals. Comparison between different routes of administration showed that local injections of colchicine are needed to reveal optimally immunoreactive perikarya in nuclei located far from the ventricles. Met-enkephalin-containing fibres and terminals are widely distributed in the posterior brain and spinal cord. The densest network of immunoreactive fibers are observed in the superficial layers of the cervical spinal cord and the caudal trigeminal nucleus, in the nucleus of the solitary tract, the nucleus of the facial nerve, the nucleus of the prepositus hypoglossi, the nucleus raphe pallidus, the medial vestibular nucleus, the interpedoncular nucleus and the substantia nigra. A moderate staining of fibres is observed in various nuclei including the ventral horn of the spinal cord and caudal trigeminal nucleus, the brainstem and midbrain reticular formation, the inferior olivary complex, the nucleus of the descending trigeminal tract and the periaqueductal grey. Met-enkephalin-containing perikarya are present in all the nuclei cited before, except in the inferior olivary complex. The densest aggregation of enkephalin-like perikarya is observed in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, nucleus reticularis gigantocellularis pars alpha and nucleus reticularis lateralis. The general distribution of enkephalin-containing structures in the cervical spinal cord, brainstem and midbrain of the cat appears very similar to that of the rat except in the substantia nigra where met-enkephalin cell bodies are found in the cat but not in the rat. In particular the pain-related nuclei present a similar distribution of the peptide in the two species; however, met-enkephalin-containing cell bodies are much more numerous in the cat than in the rat (notably in the reticular formation). Similar types of met-enkephalin innervation occur in the dorsal and intermediate grey of the spinal cord and of the caudal trigeminal nucleus supporting further that the functional organizations of these regions are closely related.

Animals↗