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M Hamon

Publications and source records attributed to M Hamon.

At least 307 records · Page 17Linked to original sources
PubMed1992

Kappa-/mu-receptor interactions in the opioid control of the in vivo release of substance P-like material from the rat spinal cord.

The possible involvement of mu and kappa receptors in the opioid control of the spinal release of substance P-like material was assessed in vivo, in halothane-anaesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid receptor agonists and antagonists. Whereas the intrathecal perfusion with the mu agonist DAGO (10 microM) significantly enhanced (approximately + 50%) the spontaneous release of substance P-like material, that with the kappa agonist U 50488 H (10 microM) produced no change in the peptide outflow. The respective antagonists naloxone (10 microM) for the mu receptors and nor-binaltorphimine (10 microM) for the kappa receptors did not affect the spontaneous release of substance P-like material, indicating that endogenous opioids acting at mu and kappa receptors do not exert a tonic control on substance P-containing neurons in the spinal cord of halothane-anaesthetized rats. However, as expected from the involvement of mu receptors, the stimulatory effect of DAGO on the peptide outflow could be prevented by naloxone but not norbinaltorphimine. Furthermore, instead of an increase with DAGO alone, a significant decrease in the spinal release of substance P-like material was observed upon the intrathecal perfusion with DAGO plus U 50488 H. Additional experiments with the respective mu and kappa antagonists naloxone and nor-binaltorphimine demonstrated that this effect actually resulted from the simultaneous stimulation of mu and kappa receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Quantification of 5-hydroxytryptamine1A receptors in the cerebellum of normal and X-irradiated rats during postnatal development.

5-Hydroxytryptamine1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [1251]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [3H]8-OH-DPAT specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine1A sites per mg membrane protein (Bmax) was higher in X-irradiated animals than in age-paired controls. However, on a "per cerebellum" basis, no significant difference could be detected between the total number of 5-hydroxytryptamine1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine1A receptors are not located on developing granule cells. The progressive decrease in 5-hydroxytryptamine1A receptor density during the first postnatal month did not reflect a transient expression of 5-hydroxytryptamine1A receptors in the cerebellum of newborn rats, but resulted from the progressive "dilution" of these sites in this growing structure. The higher density of 5-hydroxytryptamine1A sites in X-irradiated rats simply reflected a lower "dilution" due to the delayed growth of the cerebellum in these animals.

Aging↗
PubMed1992

In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle.

The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.

Animals↗
PubMed1992

Determination of thevetin B in serum by fluorescence polarization immunoassay.

Thevetin B, a cardiac glycoside of Thevetia neriifolia Juss. seeds, was determined in serum by fluorescence polarization immunoassay. Anti-digitoxin antibody was used, thevetin B genin being structurally identical to digitoxigenin. Cross-reactivity of 94% was found by this method, for concentrations from 5 to 80 ng ml-1.

Cardenolides↗
PubMed1992

Proto-oncogene expression in rabbit aorta after wall injury. First marker of the cellular process leading to restenosis after angioplasty?

In order to study the earliest phenomenons occurring in the arterial wall after balloon angioplasty, the level of expression of the proto-oncogenes, c-fos and c-myc, was studied in rabbit aorta after balloon denudation by using Northern blot analysis. Both c-fos and c-myc are rapidly and transitorily induced (maximal at 30 min and 2 h after mechanical injury for c-fos and c-myc respectively). By comparison, infusion of norepinephrine increases oncogene expression in normal non-denuded rabbit aorta after 1 h, but the combination of both mechanical and hormonal stimuli do not lead to a more important induction than balloon denudation alone.

Angioplasty, Balloon↗
PubMed1992

Anxiolytic-like actions of anpirtoline in a mouse light-dark aversion paradigm.

The anxiolytic-like potential of anpirtoline was assessed in a mouse light/dark aversion test. Anpirtoline (1.0 ng kg(-1)-1.0 micrograms kg-1 i.p.) reduced the aversive responding of mice. This was detected as an increase in the latency to locate the non-aversive compartment and by decreases in the percentage of the time spent in the dark compartment, and the numbers of rears and line crossings in the dark compartment. In radioligand binding studies anpirtoline displayed submicromolar affinity for 5-HT1A, 5-HT1B and 5-HT3 receptor recognition sites (Ki = 151, 28 and 30 nM, respectively) and more modest affinity for 5-HT2 receptor recognition sites (Ki = 1.48 microM). It is concluded that anpirtoline has a unique spectrum of affinity for 5-HT receptor subtypes, its interaction with which may account for its anxiolytic-like activity.

Animals↗
PubMed1992

Opioid control of the in vitro release of cholecystokinin-like material from the rat substantia nigra.

Possible interactions between Met-enkephalin and cholecystokinin (CCK)-containing neurons in the rat substantia nigra were investigated by looking for the effects of various opioid receptor ligands and inhibitors of enkephalin-degrading enzymes on the K(+)-evoked overflow of CCK-like material (CCKLM) from substantia nigra slices. The delta-opioid agonists D-Pen2, D-Pen5-enkephalin (50 microM) and Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET; 3 microM) enhanced, whereas the mu-opioid agonists Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO; 10 microM) and MePhe3, D-Pro4-morphiceptin (PL 017; 10 microM) decreased, the K(+)-evoked release of CCKLM. By contrast, the kappa-opioid agonist U-50488 H (5 microM) was inactive. The stimulatory effect of DTLET could be prevented by the delta antagonist ICI-154129 (50 microM), but not by the mu antagonist naloxone (1 microM). Conversely, the latter drug, but not ICI-154129, prevented the inhibitory effect of DAGO and PL 017. A significant increase in CCKLM overflow was observed upon tissue superfusion with the peptidase inhibitors kelatorphan or bestatin plus thiorphan. This effect probably resulted from the stimulation of delta-opioid receptors by endogenous enkephalins protected from degradation, because it could be prevented by ICI-154129 (50 microM). Furthermore the peptidase inhibitors did not enhance CCKLM release further when delta-opioid receptors were stimulated directly by DTLET (3 microM). These data indicate that opioids acting on delta and mu receptors may exert an opposite influence, i.e., excitatory and inhibitory, respectively, on CCK-containing neurons in the rat substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pharmacological and physicochemical properties of pre-versus postsynaptic 5-hydroxytryptamine1A receptor binding sites in the rat brain: a quantitative autoradiographic study.

Numerous data suggested that the pharmacological and biochemical properties of 5-hydroxytryptamine1A (5-HT1A) receptors exhibit some regional differences in the CNS, notably within the raphe nuclei compared with various forebrain areas (such as the hippocampus). This possibility has been further investigated in the dorsal raphe nucleus and two areas within the hippocampus, the dentate gyrus and the CA1 area, using the quantitative autoradiographic technique. The potencies of 5'-guanylylimidodiphosphate to inhibit the specific binding of 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)tetralin (125I-BH-8-MeO-N-PAT) to 5-HT1A sites and of N-ethylmaleimide to block these sites irreversibly were identical in the dorsal raphe nucleus and the hippocampal areas in rat brain sections. In contrast, slight but significant differences were noted in the pH dependence and pharmacological properties of 5-HT1A sites labeled by 125I-BH-8-MeO-N-PAT in these three regions. Similarly, heat denaturation experiments and tissue exposure to either phospholipase A2 or the alkylating agent 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetraline revealed regional differences in the properties of 5-HT1A sites. However, in most cases, the observed variations were of greater amplitude between the CA1 area and the dentate gyrus, where 5-HT1A sites are located postsynaptically, than between any one of these areas and the dorsal raphe nucleus where they act as (presynaptic) somatodendritic autoreceptors. These data further support that subtypes of 5-HT1A receptors probably exist in the rat brain, but this heterogeneity seems unrelated to the pre- or post-synaptic location of these receptors.

Alkylating Agents↗
PubMed1992

Anpirtoline, a novel, highly potent 5-HT1B receptor agonist with antinociceptive/antidepressant-like actions in rodents.

1. The purpose of the present study was to relate the effects of the novel drug, anpirtoline, on 5-hydroxytryptamine (5-HT) receptor subtypes to its antinociceptive and antidepressant-like actions in rodents. 2. Binding assays with rat brain membranes have shown that anpirtoline bound with a much higher affinity to 5-HT1B receptor (Ki = 28 nM) than to 5-HT1A (Ki = 150 nM) and 5-HT2 (Ki = 1.49 microM) receptors. 3. Like 5-HT, anpirtoline concentration-dependently inhibited forskolin-stimulated adenylate cyclase activity in homogenates from the rat substantia nigra. Both effects were not additive, and could be prevented by 5-HT1B receptor antagonists such as propranolol and penbutolol. 4. In superfused rat and pig brain cortex slices preincubated with [3H]-5-HT, the electrically evoked tritium overflow was inhibited by anpirtoline and 5-HT. Whereas 5-HT was equipotent in both tissues (EC50 = 69 nM), anpirtoline was markedly less potent in pig brain cortex slices (EC50 = 1190 nM) than in rat brain cortex slices (EC50 = 55 nM). The concentration-response curve for anpirtoline was shifted to the right by metitepine in both preparations. 5. In the social behaviour deficit test, anpirtoline and trifluoromethylphenyl-piperazine were effective in reversing the isolation-induced impairments in mice, an effect shown only by compounds with agonist properties at the 5-HT1B receptor. 6. In the electrostimulated pain test using mice, anpirtoline dose-dependently increased the pain threshold with an ED50 of 0.52 mg kg-1, i.p. The antinociceptive activity of anpirtoline was abolished by pretreatment with cyproheptadine or propranolol.7. In the forced swimming test in rats, anpirtoline induced a dose-related increase in swimming activity. With an ED50 value of 4.6mgkg-1, i.p., anpirtoline was 4 times more potent than the two standard compounds imipramine and desipramine. The decrease of immobility time or the increase of active periods in this model of behavioural despair is suggested to be characteristic of antidepressant drugs.8. Anpirtoline exhibits both antinociceptive and antidepressant-like activities in animals. It is probable that anpirtoline elicits these pharmacological effects via its agonist effect on 5-HT1B and 5-HT1A receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Trophic effects of neurotransmitters during brain maturation.

Besides their neurotransmitter and/or neuromodulatory roles, many neuroactive substances synthesized and released during brain development can also directly influence neuronal differentiation. Transitory expression of neurotransmitters, their metabolic enzymes and their receptors is only one aspect of this trophic role. The most considerable progress in neurotrophic factor research has been made with the use of primary cultures of neuronal cells, and numerous studies have focused on the effects of neurotransmitters on the differentiation of cells at various stages of development. Thus, several neuropeptides like VIP, substance P, enkephalins, somatostatin, and monoamines, can modulate neuronal differentiation, but only during a limited period of fetal life. Among the monoamines, it was shown that, depending on the target, 5-HT stimulates the development of the neuropile, the myelinization of axons, the differentiation of the synaptic contacts, induces markers of monoaminergic neuron differentiation, inhibits the development of the growth cone, decreases the branching of neurites, and influences the survival, cell body size, and neurite outgrowth in several neuronal cultures. 5-HT can also indirectly influence the differentiation of serotonergic neurons by the intermediate of astrocytes, and it was shown in our laboratory that 5-HT1A agonists can stimulate the cholinergic parameters of primary cultures of rat fetal septal neurons. At the molecular level, the events triggered by neurotransmitters that underlie their neurotrophic action probably involve the transmembrane influx of calcium. To date, calcium regulation of cellular processes is one of the most rapidly expanding areas of research in developmental neurobiology.

Animals↗
PubMed1992

[Determination of mannitol and lactulose in urine by capillary gas chromatography].

Gas capillary chromatography (GCC) determination of mannitol and lactulose in urine after oral intake is a method for assessing the intestinal permeability in various bowel diseases. The method proposed, using gas capillary chromatography with flame ionization detection after silylation of urine residue, gives good results: coefficients of variation varied from 6 to 8.7% for mannitol and 7.5 to 13.7% for lactulose. Detection limit was 5 mg/l for both compounds.

Flame Ionization↗
PubMed1991

Involvement of tryptophan residue(s) in the specific binding of agonists/antagonists to 5-HT3 receptors in NG108-15 clonal cells.

Chemical modification of the 5-HT3 receptors in membranes from NG108-15 hybridoma cells was achieved using protein modifying reagents specific for various amino acid residues: N-bromosuccinimide for tryptophan, dithiothreitol for cystine, sodium tetrathionate for cysteine, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline for aspartic and glutamic acids, diethylpyrocarbonate for histidine, tetranitromethane for tyrosine and 2,3-butanedione for arginine. Among all the reagents tested, N-bromosuccinimide produced the largest alteration in the specific binding of [3H]zacopride onto 5-HT3 receptors. A significant reduction in Bmax (approximately 50%) with no change in Kd were noted on [3H]zacopride specific binding to membranes which were incubated with 40 microM N-bromosuccinimide for 60 min at 25 degrees. The occupancy of 5-HT3 receptor binding sites by various 5-HT3 agonists and antagonists (phenylbiguanide, ondansetron, granisetron, MDL 72222) prevented, at least partially, any subsequent reduction in [3H]zacopride specific binding by N-bromosuccinimide treatment. However, neither m-chloro-phenylbiguanide, among the agonists, nor zacopride, among the antagonists, were able to prevent the effect of N-bromosuccinimide, suggesting that variations might exist in the molecular mechanisms implicated in the binding of 5-HT3 ligands to the recognition site on 5-HT3 receptors. Nevertheless, these data support the suggestion that tryptophan residue(s) are probably involved in the binding of agonists and antagonists onto 5-HT3 receptors in NG108-15 cell membranes.

Amino Acids↗
PubMed1991

Opioid control of the release of Met-enkephalin-like material from the rat spinal cord.

The possible control by opioids of the release of Met-enkephalin-like material (MELM) from the rat spinal cord was investigated in vitro and in vivo. Superfusion of slices of the dorsal zone of the lumbar enlargement with the mu selective agonists DAGO or PL 017 or the delta selective agonist DTLET produced a significant reduction in the K(+)-evoked MELM release from these tissues. These effects persisted in the presence ot tetrodotoxin, as expected from their mediation through presynaptically located opioid autoreceptors. Furthermore, the inhibitory effect of DAGO and PL 017, but not that of DTLET, was prevented by the preferential mu antagonist naloxone. Conversely, the effect of DTLET was prevented by the delta antagonist naltrindole but not by naloxone. In vivo experiments performed in halothane-anaesthetized rats have shown that the intrathecal perfusion of DAGO and DTLET significantly depressed the spontaneous MELM outflow from the whole spinal cord. In contrast to these mu and delta agonists, the kappa selective agonist U 50488 H did not affect the in vivo- and only slightly reduced (at a very high concentration: 50 microM) the in vitro-release of MELM from the rat spinal cord. These data indicate that both mu and delta opioid autoreceptors are involved in a local presynaptic autoinhibitory control of MELM release in the rat dorsal horn.

Animals↗
PubMed1991

[3H]5-methyl-urapidil labels 5-HT1A receptors and alpha 1-adrenoceptors in the rat CNS. In vitro binding and autoradiographic studies.

The tritiated derivative of the potent antihypertensive agent, 5-methyl-urapidil, was used as a radioligand in binding studies with rat brain membranes and tissue sections. Serotonin and prazosin inhibited [3H]5-methyl-urapidil binding to membranes from the rat hippocampus, cerebral cortex and brainstem biphasically, leading to the definition of serotonin high-affinity and prazosin high-affinity [3H]5-methyl-urapidil binding sites. Comparison of these serotonin-sensitive [3H]5-methyl-urapidil binding sites with the 5-HT1A sites labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) revealed striking similarities regarding pharmacological properties, respective densities and regional distribution. On the other hand, the prazosin-sensitive [3H]5-methyl-urapidil binding sites should correspond to the alpha 1A-subtype of adrenoceptors which has recently been defined. Detailed autoradiographic investigations allowed the detection of 5-HT1A sites labelled by both [3H]5-methyl-urapidil and [3H]8-OH-DPAT in the posterior raphe nuclei (pallidus and obscurus) which are possibly involved in the hypotensive action of 5-methyl-urapidil. These data demonstrate that [3H]5-methyl-urapidil is a useful radioligand for the visualization and quantification of both 5-HT1A serotonin receptors and alpha 1A-adrenoceptors in the central nervous system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Dopamine increases the expression of tyrosine hydroxylase and aromatic amino acid decarboxylase in primary cultures of fetal neurons.

Previous studies, aimed at identifying which diffusible signals may influence the differentiation of embryonic neurons towards the monoaminergic phenotypes during brain development, have shown that serotonin itself could promote the 'serotoninergic-like properties' of hypothalamic cells from mouse embryos. We presently reinvestigated such 'autocrine/paracrine' regulatory mechanisms by exposing dissociated cell cultures from embryonic rat hypothalamus and brain stem to dopamine--or related agonists--in an attempt to influence their differentiation towards the catecholaminergic phenotype. Chronic treatment of cells by dopamine or apomorphine (a mixed D1/D2 agonist), but not selective D1 and D2 agonists, significantly increased the number of cells that expressed tyrosine hydroxylase (TH: as assessed with a specific anti-TH antiserum) and the activity of aromatic L-amino acid decarboxylase (AADC) in the cultures. Furthermore, apomorphine treatment also decreased the levels of cholecystokinin-like material in primary cultures from the brainstem (but not the hypothalamus) where both dopamine and cholecystokinin are--partly--colocalized in mesencephalic dopaminergic neurons. The maximal effects of both dopamine and apomorphine on TH expression and AADC activity occurred earlier in the brainstem (on cells from 14- to 15-day-old embryos) than in the hypothalamus (on cells from 15- to 16-day-old embryos), in line with the well established caudo-rostral maturation of the rat brain. Furthermore both the expression and the dopamine-induced modulation of AADC activity and TH immunoreactivity appeared to occur independently of each other. Present and previous data are in agreement with a possible autocrine/paracrine action of dopamine and serotonin during brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential inhibitory/stimulatory modulation of spinal CCK release by mu and delta opioid agonists, and selective blockade of mu-dependent inhibition by kappa receptor stimulation.

Opioid-cholecystokinin (CCK) interactions at the spinal level were investigated by looking for possible modulations by various opioid agonists of the release of cholecystokinin-like material (CCKLM) from slices of the dorsal zone of the rat lumbar enlargement. K(+)-evoked CCKLM overflow was reduced by 0.1-10 microM of the mu agonist DAGO or 10 nM to 3 microM of the delta agonist DTLET. By contrast, at a higer concentration (10 microM), the latter drug as well as morphine enhanced CCKLM overflow. Although inactive alone, the kappa opioid agonist U 50488 H (1 microM) prevented the inhibitory effect of DAGO without affecting that of DTLET. These data suggest that an opioid acting through the stimulation of mu, delta and kappa receptors (such as morphine) should produce a net increase in the spinal release of CCK.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Is substance P released from slices of the rat spinal cord inactivated by peptidase(s) distinct from both 'enkephalinase' and 'angiotensin-converting enzyme'?

Studies on the effects of peptidase inhibitors on substance P-like immunoreactive material (SPLI) released by K(+)-induced depolarization from slices of the rat spinal cord showed that bacitracin was the most potent agent to protect SPLI from degradation. Captopril and thiorphan which inhibit, respectively, angiotensin I converting enzyme and endopeptidase-24.11 also protected SPLI from degradation. However other inhibitors of these two enzymes, kelatorphan for endopeptidase-24.11 and enalaprilat for angiotensin I converting enzyme were essentially inactive, indicating that both enzymes are probably not involved in the degradation of endogenous substance P. Instead, the non-additive protecting effect of bacitracin, captopril and thiorphan might be due to the blockade of some 'bacitracin-sensitive enzyme' playing a key role in the catabolism of SP within the rat spinal cord.

Angiotensin-Converting Enzyme Inhibitors↗