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J M Launay

Publications and source records attributed to J M Launay.

At least 73 records · Page 4Linked to original sources
PubMed1997

Apolipoprotein E gene polymorphism in early and late onset bipolar patients.

To explore the involvement of apolipoprotein E gene (APO E) in major depression, we studied the APO E gene polymorphism in a sample of 156 unrelated bipolar patients and 91 healthy volunteers. This population was stratified for age at onset of the affective disorder (onset before 18 years, after 45 years and between 18 and 45 years). Early onset bipolar patients with psychotic symptoms exhibited a significant increase of epsilon4 allele frequency (28.9%) compared to either other bipolar patients (13.1%, chi2 = 6.52, df = 1, P < 0.02) or controls (12.1%, chi2 = 7.01, df = 1, P < 0.01). The association between epsilon4 and early onset bipolar disorder (BPD) with psychotic symptoms suggests that APO E gene is a risk factor for a subgroup of BPD, or influences the phenotypic expression (i.e. psychotic symptoms or age at onset) of manic depressive illness.

Adult↗
PubMed1997

Effects of past history of major depression on smoking characteristics, monoamine oxidase-A and -B activities and withdrawal symptoms in dependent smokers.

Past history of major depression is more common in smokers than in non-smokers. We have shown in a previous study that lifetime prevalence of major depression is higher in dependent smokers and they have lower monoamine oxidase-A and -B activities than non-smokers. Because several studies have found an association between MAO-B activity and depression we analysed data of these smokers to assess whether past history of major depression is associated with reduced monoamine oxidase activities (A and B) or not. Further, we tried to characterize smokers with past history of major depression and its effect on withdrawal symptoms. The data of 88 dependent smokers (Fagerström Tolerance Questionnaire score > or = 6 and smoking > or = 20 cigarettes/day) who participated in a smoking cessation study were analysed. Smokers with past history of major depression but without current illness did not differ in demographic and smoking characteristics from smokers without past history of major depression. Smokers with past history of major depression were mainly women and had lower body mass index. Adjusted for gender and body mass index dependent smokers with or without past history of depression had similar MAO-A and MAO-B activities but smokers with past history of major depression had significantly lower resting plasma norepinephrine levels. Smokers with past history of depression had not significantly higher ratings for depression (Montgomery-Asberg Depression Rating Scales) and anxiety (Hamilton Anxiety Scales) and smoking cessation did not exacerbate these ratings (assessed up to 3 months) and none had depressive episode during the postcessation period up to one year. Past history of depression was associated with higher scores on 'expressed sadness' and 'depressive mood'. Abstinent smokers with past history of depression had significantly higher ratings in one of the seven ratings of a 6 months period for craving (day 28), anxiety (day 7) and total withdrawal symptom score (day 7) when compared to those who had no past history of major depression. It is concluded that (i) past history of major depression is more frequent in female smokers; (ii) smokers with past history of depression may have more intense withdrawal symptoms (craving and anxiety) at some time after cessation: and (iii) past history of depression does not affect monoamine oxidase activities, therefore, reduced monoamine oxidase activities found in previous studies are possibly characteristic features of smoking.

Adult↗
PubMed1997

Genetic factors regulate processes related to anxiety in mice.

The propensity for anxiety-related behavior has been studied by comparing two highly inbred strains of mice, ABP/Le and C57BL/6ByJ, in two behavioral procedures, open-field and light-dark preference. Their Mendelian F2 population allowed us to evaluate the putative involvement of four easily identifiable loci in anxiogenic processes. In fact, chromosomal regions containing the brown, pink-eyed dilution and short-ear loci on the 4th, 7th and 9th chromosomes respectively are associated with anxiety-related behavior patterns. In addition, binding of [3H]flumazenil to brain GABA(A) receptors was measured as a biochemical index that may be associated with observed behavior patterns.

Animals↗
PubMed1997

Endothelin expression in human megakaryoblastic leukemia cell lines and normal platelet precursors.

The aim of the present investigation was to determine whether endothelin (ET) could be expressed in and released from the human leukemia megakaryoblastic cell lines HEL, MEG-01, DAMI and the normal human platelet progenitors. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) on total RNA isolated from the cells, we amplified a cDNA of the expected size (453 bp). Southern-blotting hybridization revealed that RT-PCR products from the cell lines were specific of ET-1 mRNA. Immunocytochemical analyses highlighted immunoreactive ET-1 in the cytoplasm of these cells which also released the mature peptide. ET-1 release from the three cell lines was increased by thrombin exposure. Although MEG-01 cells express ET receptors, ET-1, the selective ETB agonist sarafotoxin 6C and the non-selective ET-receptor antagonist PD 142893 showed no proliferative or antiproliferative action in basal or stimulating medium. This indicated a lack of autocrine ET-mediated effect on growth. These results demonstrate for the first time that human megakaryoblastic leukemia cell lines and normal bone marrow platelet precursors express ET-1 mRNA and release the mature peptide.

Blood Platelets↗
PubMed1997

Oxidation, nitrosation, and nitration of serotonin by nitric oxide-derived nitrogen oxides: biological implications in the rat vascular system.

Because NO is not very reactive in an oxygen-free buffer, a significant part of serotonin (5-HT) is transformed by NO in nondeaerated phosphate buffer, at pH 7.4, into (4-serotonyl)-4-serotonin, 4-nitrososerotonin, and 4-nitroserotonin. Dimerization and above all nitrosation occur through the HNO2 reaction in the pH 4-6 range, possibly via radical mechanism involving N2O3. 5-HT is readily a substrate for nitrosation by HNO2 or N2O3, whereas tyrosine was described as not very reactive under the same conditions. Peroxynitrite converts 5-HT to the (4-serotonyl)-4-serotonin and to the 4-nitro derivative. In order to evaluate whether such structural modifications could modulate the biological properties of 5-HT, arterial pressure was measured after i.v. bolus injection of these derivatives to anesthetized rats. Injections of the 4-nitroso- and 4-nitro-5-HT resulted in first a brief hypotensive response and did not give the subsequent hypertensive and hypotensive phases observed with 5-HT. Finally, when tested on some cloned rat 5-HT receptors stably transfected into LMTK- cells, both 4-nitroso and 4-nitro derivatives behaved as agonists and antagonists toward 5-HT1B and 5-HT2B receptors, respectively.

Animals↗
PubMed1997

Convulsive effects of a benzodiazepine receptor inverse agonist: are they related to anxiogenic processes?

The linkage-testing strain of ABP/Le mice carries six mutations which express in easily identifiable phenotypes. By crossing this strain with a traditional inbred strain (C57BL/6ByJ) which is the 'wild type' for the mutated ABP/Le loci, we produced Mendelian populations, intercrosses and backcrosses so as to estimate whether the sensitivity to methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine receptor inverse agonist, and anxiety-related behaviour could be related to a common genetically determined substrate. We have shown that one locus on chromosome 9 is associated with beta-CCM-induced seizures and three loci on chromosomes 4, 7 and 9 are associated with anxiogenic processes. Analysis of [3H]flumazenil binding suggested a possible involvement of a Bmax decrease in both beta-CCM-induced seizures and anxiogenic processes. The putative common genetic regulation of both mechanisms is discussed.

Animals↗
PubMed1997

Treatment with 5-HT potentiates development of pulmonary hypertension in chronically hypoxic rats.

The aim of this study was to investigate the potential role of 5-hydroxytryptamine (5-HT) on development of pulmonary hypertension during chronic exposure to mild (15% O2) and severe (10% O2) hypoxia. In isolated lungs from normoxic rats preconstricted with U-46619, 5-HT (10(-12)-10(-8) M) induced dose-dependent vasodilation (n = 6), which was suppressed by the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10(-4) M, n = 5) and reduced by the 5-HT3-receptor antagonist MDL-7222 (10(-5) M, n = 6). The vasoconstriction that was observed with higher concentrations of 5-HT (10(-7)-10(-4) M) was inhibited by ketanserin (10(-5) M) and methiothepin (10(-5) M, n = 6 each). The vasodilator response to 5-HT was suppressed in lungs from rats exposed to 10% O2 but not 15% O2 (n = 6 each). In conscious rats, intravenous administration of 5-HT potentiated the pulmonary pressor response to acute hypoxia (10% O2, n = 5), an effect that remained unchanged after pretreatment with a 5-HT1 and a 5-HT2 antagonist (n = 4) but was attenuated after treatment with the cyclooxygenase inhibitor meclofenamate (n = 4). Treatment with 5-HT (5 nmol/h i.v. by osmotic pumps) for 2 wk in rats simultaneously exposed to 10% O2 increased pulmonary arterial pressure, right ventricular hypertrophy, and muscularization of pulmonary vessels in comparison with their hypoxic controls (n = 12 each). No changes occurred in 15% O2 hypoxic rats (n = 12 each). The present findings show that 5-HT potentiates development of pulmonary hypertension in rats exposed to chronic hypoxia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

NE inhibits cerebrovascular mast cell exocytosis induced by cholinergic and peptidergic agonists.

Autonomic and sensory nerves frequently contact mast cells contained in rabbit leptomeningeal arteries. We have previously shown that parasympathetic and peptidergic neurotransmitters can stimulate mast cell granule exocytosis and serotonin (5-HT) release. In the present study, we examined ex vivo the possible action of the main sympathetic neurotransmitter, norepinephrine (NE), on this exocytotic process. NE, which had no effect on mast cell 5-HT content per se, totally inhibited carbachol-induced 5-HT release and partially reduced neuropeptide-induced 5-HT release. Pretreatment with the alpha 1-adrenergic blocker did not affect the inhibitory effect of NE. Pretreatment with specific beta 1- or beta 2-adrenergic blockers antagonized this action, but the beta 2-blocker exerts a more specific dose-dependent antagonism. Together with our previous data, these results indicate that the equilibrium between autonomic and sensory nerves may determine the release of 5-HT from mast cells (parasympathetic and sensory nerves can trigger exocytosis while the sympathetics can inhibit it). Such a mechanism could be implicated in pathophysiological events in which autonomic dysfunction is likely to be involved, such as vascular headache or other phenomena involving inflammation.

Adrenergic Antagonists↗
PubMed1997

5-HT2B receptor-mediated serotonin morphogenetic functions in mouse cranial neural crest and myocardiac cells.

During embryogenesis, serotonin has been reported to be involved in craniofacial and cardiovascular morphogenesis. The detailed molecular mechanisms underlying these functions, however remain unknown. From mouse and human species, we have recently reported the cloning of 5-HT2B receptors which share signal transduction pathways with other 5-HT2 receptor subtypes (5-HT2A and 5-HT2C). In addition to phospholipase C stimulation, it appears that these three subtypes of receptor transduce a common serotonin-induced mitogenic activity, which could be important for cell differentiation and proliferation. We have first investigated the expression of 5-HT2 receptor mRNAs in the mouse embryo. Interestingly, a peak of 5-HT2B receptor mRNA expression was detected 8-9 days postcoitum, whereas there was only low level 5-HT2A and no 5-HT2C receptor mRNA expression at this stage. Expression of this receptor was confirmed by binding assays using a 5-HT2-specific ligand which revealed a peak of binding to membrane preparations from 9 days postcoitum embryos. In addition, whole mount in situ hybridisation and immunohistochemistry on similar stage embryos detected 5-HT2B expression in neural crest cells, heart myocardium and somites. The requirement for functional 5-HT2B receptors between 8 and 9 days postcoitum is supported by culture of embryos exposed to 5-HT2-specific ligands; 5-HT2B high-affinity antagonist such as ritanserin, induced morphological defects in the cephalic region, heart and neural tube. These antagonistic treatments interfere with cranial neural crest cell migration, induce their apoptosis, and are responsible for abnormal sarcomeric organisation of the subepicardial layer and for the absence of the trabecular cell layer in the ventricular myocardium. This report indicates for the first time that 5-HT2B receptors are actively mediating the action of serotonin on embryonic morphogenesis, probably by preventing the differentiation of cranial neural crest cells and myocardial precursor cells.

Animals↗
PubMed1996

Ras involvement in signal transduction by the serotonin 5-HT2B receptor.

The family of serotonin 5-HT2 receptors stimulates the phospholipase C second messenger pathway via the alpha subunit of the Gq GTP-binding protein. Here, we show that agonist stimulation of the 5-HT2B receptor subtype stably expressed in the mouse fibroblast LMTK- cell line causes a rapid and transient activation of the proto-oncogene product p21ras as measured by an increase in GTP-bound Ras in response to serotonin. Furthermore, 5-HT2B receptor stimulation activates p42mapk/p44mapk (ERK2/ERK1) mitogen-activated protein kinases as assayed by phosphorylation of myelin basic protein. Antibodies against p21ras, Galphaq, -beta, or -gamma2 subunits of the GTP-binding protein inhibit MAP kinase-dependent phosphorylation. The MAP kinase activation is correlated with a stimulation of cell division by serotonin. In addition to this mitogenic action, transforming activity of serotonin is mediated by the 5-HT2B receptor since its expression in LMTK- cells is absolutely required for foci formation and for these foci to form tumors in nude mice. Finally, we detected expression of the 5-HT2B receptor in spontaneous human and Mastomys natalensis carcinoid tumors and, similar to the 5-HT2B receptor transfected cells, the Mastomys tumor cells are also responsive to serotonin with similar coupling to p21ras activation.

Amphetamines↗
PubMed1996

A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures.

The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5-60 mg/kg dose range, beta-CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to beta-CCM. Both the Ta gene and the TaTfm/Gnc genetic background were involved in the high resistance to beta-CCM. In addition, concentrations of neurosteroids and benzodiazepine binding, both modulating GABAA receptor efficacy, have been measured in order to elucidate the biological mechanisms of drug resistance.

Animals↗
PubMed1996

The mouse 5-HT2B receptor: homologous subtype or species variant?

The recently characterized 5-HT2B subfamily of serotonin receptors has now been reported from three different species: human, rat and mouse. Their genomic structures include 2 introns present at identical positions. Despite this similarity, their respective protein sequences show some diversities. In addition, the pharmacology of these receptors is distantly related, and their sites of expression vary amongst species. Thus, it appears difficult at present to unambiguously classify these receptors into the same subfamily, raising the possibility of the existence of other 5-HT2B-like receptors, yet to be discovered.

Animals↗
PubMed1996

Immunological aspects of migraine.

The physiopathology of migraine is still largely unknown. The author reviews the changes of immunoglobulins (especially IgE), complement fractions, mediators, cytokines and inflammatory cells published in the literature. An IgE mechanism seems to be unimportant in the process of food-induced migraine. Increasing arguments for the reciprocal modulation of the brain and immune system are also reviewed as the close links between interleukins and the sensory neuromediators. However, it is presently too early to implicate a definite immunological mechanism in the physiopathogeny of migraine.

Anti-Asthmatic Agents↗
PubMed1996

Sequential onset of three 5-HT receptors during the 5-hydroxytryptaminergic differentiation of the murine 1C11 cell line.

1. The murine 1C11 clone, which derives from a multipotential embryonal carcinoma cell line, has the features of a neuroectodermal precursor. When cultured in the presence of dibutyryl cyclic AMP, the 1C11 cells extend bipolar extensions and express neurone-associated markers. After 4 days, the resulting cells have acquired the ability to synthesize, take up, store and catabolize 5-hydroxytryptamine (5-HT). We have thus investigated the presence of 5-HT receptors during the 5-hydroxytryptaminergic differentiation of this inducible 1C11 cell line. 2. As shown by the binding of [125I]-GTI and the CGS 12066-dependent inhibition of the forskolin-induced cyclic AMP production, functional 5-HT1B/1D receptors become expressed on day 2 of 1C11 cell differentiation. The density of these receptors remained unchanged until day 4. 3. The same holds true for the 5-HT2B receptor, also identified by its pharmacological profile and its positive coupling to the phosphoinositide cascade. 4. On day 4 of 1C11 cell differentiation, a third 5-HT receptor, pharmacologically and functionally similar to 5-HT2A, had become induced. 5. Strikingly, the amounts of each transcript encoding 5-HT1B, 5-HT2A and 5-HT2B receptor did not very significantly during the time course of the 1C11 5-hydroxytryptaminergic differentiation. 6. The clone 1C11 may thus provide a useful in vitro model for studying regulation(s) between multiple G-linked receptors as well as the possible role of 5-HT upon the expression of a complete 5-hydroxytryptamine phenotype.

Animals↗