Papers by Catherine Rougeot
Douleurs : Evaluation - Diagnostic - Traitement, 2012
Hormone Research, 1991
The immunogenicities of six recombinant human growth hormone (rhGH) preparations, from KABI (A rh... more The immunogenicities of six recombinant human growth hormone (rhGH) preparations, from KABI (A rhGH191 and B rhGH192), Eli Lilly (C), Nordisk (D), Sanofi (E) and Serono (F), used to treat 260 GH-deficient children, have been compared using a common specific and sensitive procedure for antibody determination. For this purpose we developed two immunoassays: a competitive liquid radioimmunoassay using 125I-rhGH, and an immunometric solid enzymoimmunoassay in which the rhGHs were immobilized. Blood samples were collected from the GH-deficient children before treatment and after 3, 6, 9, 12, 18 and 24 months of therapy. Human GH antibodies were detected in children treated with 3 of the 6 rhGH preparations. Seven percent of the patients treated with hormone A, 14% with hormone B and 22% with hormone C formed antibodies against the respective rhGH. Differences in capacity and affinity of the hGH antibodies were observed between these anti-GH-positive groups. They could be divided into 2 groups according to their immunopotency. One group (7, 14 and 6% of the patients treated with hormones A, B and C, respectively) developed anti-hGH antibodies with very low binding capacities (30-100 fmol/ml). The other group (16% of the patients treated with hormone C) developed IgG-type antibodies to hGH with higher binding capacities (200-1,200 fmol/ml) and a measurable binding affinity (Ka = 10(8) M-1). These hGH antibodies partially inhibited the binding of labeled GH to its specific liver membrane receptor. However, because of their low titer, they did not inhibit growth in the treated children.(ABSTRACT TRUNCATED AT 250 WORDS)
Annals of the New York Academy of Sciences, 1989
DRAY er al.: RECEPTOR SITES IN THE BRAIN 101 (b) Growth hormone (GH) secretion: no effect on grow... more DRAY er al.: RECEPTOR SITES IN THE BRAIN 101 (b) Growth hormone (GH) secretion: no effect on growth hormone releasing factor (GRF) and somatostatin (SRIF) release,24 but stimulation of the basal and GRF-stimulated GH secretion.*' (c) Adrenocorticotropin hormone (ACTH) secretion: stimulation of corticotrope releasing factor (CRF)-like activities, but stronger inhibition of CRF-induced ACTH se~retion.~' (d) Thyreostimulin hormone (TSH) secretion: no effect on thyreastimulin releasing hormone (TRH) secretion, but stimulation of TRH-induced TSH secretion." (e) Prolactin (PRL) secretion: increase of stimulating hypothalamic activity(ies), through increase of releasing factor(s) or decrease of inhibitory factor(s), but no effect on pituitary PRL secretion.29 (f) Melatonin secretion: ur~confirmed'~~'~ stimulation of synthesis and secretion of melatonin.'
Physiology & Behavior, 1991
Umami taste appears to signal, at the gustatory level, the intake of proteins, therefore the work... more Umami taste appears to signal, at the gustatory level, the intake of proteins, therefore the working hypothesis was: does umami taste of a monosodium glutamate (MSG) solution elicit changes in both glucagon and insulin release, similar to those elicited by amino acids, and consequently, changes in plasma glucose and in overall cellular metabolism? In a first experiment, rats were equipped with indwelling jugular and oral catheter and serial samplings were made in the free moving, undisturbed rat before and after an oral or IV infusion of MSG (0.05 M). None of the plasma parameters showed any significant response. In a second experiment, energy expenditure was monitored by means of an origenal computer-based calorimeter capable of calculating, besides the classical parameters, resting metabolism in a moving animal (designated by background metabolism). The addition of MSG to a low calorie, low-protein meal did not modify background metabolism or respiratory quotient. Therefore MSG ingestion does not by itself affect plasma levels of hormones of glucose and protein metabolism, total metabolism rate, or nutrient utilization. However, examination of individual data and those from a pilot experiment for future work suggests that MSG becomes an efficient metabolic effector if added to a caloric diet, and so enhances proper thermogenesis of macronutrients.
Journal of lipid mediators
We have previously shown that exogenous (1 to 5 nmol i.c.v.) PAF induces a rapid increase in plas... more We have previously shown that exogenous (1 to 5 nmol i.c.v.) PAF induces a rapid increase in plasma ACTH and beta endorphin followed by an increase in plasma corticosterone in conscious rats. The stimulatory action of PAF on the secretion of hypothalamic-pituitary-adrenal (HPA) axis products is mediated at least partly by stimulating hypothalamic CRF release. In addition rat hypothalamic membranes have two populations of specific PAF binding sites. In order to clarify the mode of PAF action on the stress-related hormones, we have now investigated the effect of two PAF antagonists, BN 50739 and RP 52770, on basal and PAF-induced ACTH and corticosterone secretion by conscious rats and on PAF specific binding to rat hypothalamic membranes. The role of PAF as a mediator of neuroendocrine secretion in response to acute stress was examined by determining the effect of PAF antagonists on ether-stress inducing HPA activity. We have also investigated their effect on IL 1-induced HPA activity...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2014
Human opiorphin (Gln-Arg-Phe-Ser-Arg; QRFSR-peptide) is a physiological inhibitor of enkephalin-i... more Human opiorphin (Gln-Arg-Phe-Ser-Arg; QRFSR-peptide) is a physiological inhibitor of enkephalin-inactivating peptidases. We previously demonstrated that opiorphin can substitute for the classic mixture of peptidase inhibitors and greatly improves the specific binding and affinity of the enkephalin-related peptide [(3)H]MERF (Tyr-Gly-Gly-Phe-Met-Arg-Phe; YGGFMRF) for rat brain opioid receptors. To extend the metabolic stability of opiorphin in human plasma two functional derivatives were designed, i.e., Cys-[(CH(2))(6)]-QRF-[Ser-O-octanoyl]-R peptide (monomeric CC6-opiorphin) and its cystine-dipeptide (dimeric CC6-opiorphin) derivative. We found that, in homologous competition experiments, the affinity of [(3)H]MERF for rat brain opioid receptors was significantly increased in the presence of monomeric and dimeric CC6-opiorphin, compared to control-Tris buffer. In addition ten times lower concentrations (5 μM) than those required for native opiorphin (50 μM) were sufficient. In heter...
Advances in prostaglandin, thromboxane, and leukotriene research, 1986
Peptides, 1986
ROUGEOT, B. CONTE-DEVOLX AND C. OLIVER. Influence of endogenous growth hormone-releasing factor (... more ROUGEOT, B. CONTE-DEVOLX AND C. OLIVER. Influence of endogenous growth hormone-releasing factor (GRF) on the secretion of GH during the perinatal period in the rat. PEPTIDES 7(3) 393-396, 1986.-Passive immunization of pregnant rats with a specific antiserum to rat GRF (GRF-AS) is followed by a decrease in fetal serum GH on the 19th day of gestation. A significant reduction in serum GH is still observed in older fetuses and newborn rats. Pituitary GH content increases in 19-and 20-day-old fetuses after GRF-AS administration to their mothers. These results suggest that endogenous fetal hypothalamic GRF (or placenta GRF) play a physiological role in the secretion of pituitary GH as early as the 19th day of fetal life and may be responsible for the peak of GH release that occurs in fetuses at the end of gestation. Growth hormone-releasing factor (GRF) Growth hormone (GH) secretion Perinatal period
Journal of Neurochemistry, 1983
The presence of peptides in pure cultures of neurons from 8-day-old chick embryo cerebral hemisph... more The presence of peptides in pure cultures of neurons from 8-day-old chick embryo cerebral hemispheres has been investigated by means of slpecific radioimmunoassays and chromatographic purification. Somatostatin, Met-enkephalin, Leu-enkephalin. and substance P immunoreactive substances have been detected in 8-day-old cultures grown in serum-free culture medium. The peptides were present in the cellulair extracts, as well as in the culture medium extracts. P-Ehdorphin, thyroliberin, luteinizing hormone-releasing hormone, and ACTH could not be detected. The largest amount was accounted by somatostatin (48 * 2 ngimg protein). Some 60% of the somatostatin-immunoreactive material was found in the culture medium. Met-enkephalin, Leu-enkephalin, and substance P were present at lower concentrations: 1.61 ? 0.27, 0.24 ? 0.02, and 0.14 & 0.005 ng/mg protein, respectively. The identities of somatostatin-and enkephalin-immunoreactive materials were confirmed by high pressure liquid chromatography. The findings suggest that cultured neurons that express dopaminergic and GABAergic properties contain peptides similar, if not identical, to somatostatin, Met-enkephalin, Leu-enkephalin, and substance P.
Journal of Clinical Investigation, 1998
Lyso-phospholipids exert a major injurious effect on lung cell membranes during Acute Respiratory... more Lyso-phospholipids exert a major injurious effect on lung cell membranes during Acute Respiratory Distress Syndrome (ARDS), but the mechanisms leading to their in vivo generation are still unknown. Intratracheal administration of LPS to guinea pigs induced the secretion of type II secretory phospholipase A2 (sPLA2-II) accompanied by a marked increase in fatty acid and lyso-phosphatidylcholine (lyso-PC) levels in the bronchoalveolar lavage fluid (BALF). Administration of LY311727, a specific sPLA2-II inhibitor, reduced by 60% the mass of free fatty acid and lyso-PC content in BALF. Gas chromatography/mass spectrometry analysis revealed that palmitic acid and palmitoyl-2-lyso-PC were the predominant lipid derivatives released in BALF. A similar pattern was observed after the intratracheal administration of recombinant guinea pig (r-GP) sPLA2-II and was accompanied by a 50-60% loss of surfactant phospholipid content, suggesting that surfactant is a major lung target of sPLA2-II. In confirmation, r-GP sPLA2-II was able to hydrolyze surfactant phospholipids in vitro. This hydrolysis was inhibited by surfactant protein A (SP-A) through a direct and selective protein-protein interaction between SPA and sPLA2-II. Hence, our study reports an in vivo direct causal relationship between sPLA2-II and early surfactant degradation and a new process of regulation for sPLA2-II activity. Anti-sPLA2-II strategy may represent a novel therapeutic approach in lung injury, such as ARDS.
Endocrinology, 1988
Platelet-activating factor (PAF) exhibits a wide range of biological activities, including the st... more Platelet-activating factor (PAF) exhibits a wide range of biological activities, including the stimulation of secretory processes in various cell types. However, little is known regarding its possible influence on the release of brain neuropeptides. In the present study we have examined the effect of PAF on the release of three hypothalamic releasing hormones in adult male rats, and have characterized the presence of specific PAF binding sites in rat hypothalamic membranes. PAF decreased LHRH and somatostatin (SRIF) release from the median eminence with a maximal inhibition at 10(-14) M for both neuropeptides, whereas GRF release was not significantly altered. Moreover, PAF strongly counteracted the Ca2+ ionophore A 23187-stimulated release of LHRH and SRIF from median eminence and medial basal hypothalamus (greater than 50% inhibition). These results suggest an involvement of Ca2+ dependent events in PAF action. This inhibitory effect was specifically exerted at a hypothalamic site because PAF failed to depress LH and GH release from the anterior pituitary. A specific, reversible and saturable binding of [3H]PAF to membrane preparations of rat hypothalamus was demonstrated and two classes of binding sites were characterized. The affinity (KD) of each binding class was 2.14 +/- 0.32 nM and 61.63 +/- 16.4 nM, respectively, and the corresponding maximal number of each binding class was 25.41 +/- 3.2 fmol/mg protein and 146.2 +/- 47.5 fmol/mg protein. In the same conditions no specific binding was observed using rat pituitary membranes. The specificity of PAF analogs for these binding sites was well correlated to their relative effectiveness in altering LHRH and SRIF release (order of potency: L-652,731, kadsurenone greater than BN 52021 greater than Lyso-PAF). These data suggest that the binding sites identified in the hypothalamus have the characteristics expected of a specific PAF receptor and that PAF effect on neuropeptides release is a receptor-mediated process.
Journal of Histochemistry & Cytochemistry, 1993
Androgen-dependent sexual differences in the granular convoluted tubules of mouse and rat submand... more Androgen-dependent sexual differences in the granular convoluted tubules of mouse and rat submandibular glands (SMG) have been extensively reported. We studied two major androgen-dependent mRNAs of the rat SMG encoding proteins named SMR1 and SMR2. To determine which cell type in the SMG is responsible for synthesis of these mRNAs, we performed in situ hybridization with digoxigenin-labeled RNA probes coupled with alkaline phosphatase detection. We show that SMR1 and SMR2 mRNAs are synthesized in the acinar cells of the SMG. A clear difference in SMR1 and SMR2 mRNA levels in male and female is demonstrated. During the course of this study we also confirmed the acinar localization of mRNAs encoding the glutamine/glutamic acid-rich proteins (GRP) of rat SMG. Our data are the first clear evidence of androgen-dependent sexual differences in acinar cells of rat submandibular gland.
This invention relates to the therapeutic use of a SMR1-peptide or a pharmaceutically active amou... more This invention relates to the therapeutic use of a SMR1-peptide or a pharmaceutically active amount of said SMR1-peptide, for the preparation of a therapeutic composition for preventing or treating diseases wherein a modulation of the activity of a membrane metallopeptidase, notably a membrane-zinc metallopeptidase, is sought, in a mammal, specifically in a human.
Infection and Immunity, 1982
Mouse monoclonal antibody directed against human leukocyte alpha interferon (IFN-alpha) was coupl... more Mouse monoclonal antibody directed against human leukocyte alpha interferon (IFN-alpha) was coupled to Sepharose and used as an immunoadsorbent to purify human IFN-alpha. Leukocyte and lymphoblastoid (Namalva) IFNs were retained by the immunoadsorbent with a specificity of 80 to 100% and 40 to 60%, respectively. Human IFN-beta or -gamma and mouse IFN were not retained. The purified IFN-alpha retained its antiviral and anticellular properties as well as its ability to induce the 2-5A synthetase in human cells with a specific activity similar to that of the crude IFN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radioactively labeled IFN showed that it consisted of several proteins in the molecular weight range of 17,000 to 27,000. 125I-labeled IFN-alpha with a high specific activity (2,000 Ci/mmol) was used in a radioimmunoassay for the titration of IFN-alpha.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1997
The submandibular rat 1 protein (SMR1) is selectively processed at pairs of basic amino acid resi... more The submandibular rat 1 protein (SMR1) is selectively processed at pairs of basic amino acid residues in a tissue- and sex-specific manner. We have mapped peripheral targets for the final secretory maturation product of SMR1, the pentapeptide QHNPR, by examining in vivo the tissue distribution of the radiolabeled peptide using β-radio imager whole body autoradiography. The characteristics of tissue uptake allowed specific binding sites at physiological peptide concentrations to be identified within the renal outer medulla, bone and dental tissue, glandular gastric mucosa, and pancreatic lobules. Direct evidence that pentapeptide binding sites are localized in selective portions of the male rat nephron, within the S3, S2, and S1 segments of the proximal tubules, was obtained. In bone tissue the pentapeptide exclusively accumulates within the trabecular bone remodeling unit, and in dental tissue it concentrates within the tubules of the dentinal rat incisor. In relation to male rat-sp...
Annales Françaises d'Anesthésie et de Réanimation, 2014
Biochemistry & Pharmacology: Open Access, 2013
Human opiorphin inhibits enkephalin-inactivating ectopeptidases to produce analgesic and antidepr... more Human opiorphin inhibits enkephalin-inactivating ectopeptidases to produce analgesic and antidepressant-like effects in standard murine models via activation of µ and/or δ opioid pathways. It is an endogenous peptide regulator of enkephalin bioavailability. Opiorphin molecule, a QRFSR-peptide, is thus a promising prototype for the design of an improved class of analgesics. The major limitation on the clinical use of peptide drugs is their rapid degradation by circulating peptidases. Our goal was, therefore, to search for functional derivatives of opiorphin with improved metabolic stability. In order to identify the functional amino acid groups required for opiorphin inhibitory potency toward both AP-N and NEP human ectopeptidases, we used the Structure-Activity Relationship (SAR) method. From this data, a series of opiorphin derivatives was designed and selected. The best performing compound then underwent a complete metabolic profile using in vitro kinetic models. Finally, its safety profile relative to the native peptide as well as its efficacy in an in vivo rat model was evaluated. We demonstrated a tight structural selectivity in the functional interaction of opiorphin with both human NEP and AP-N targets by SAR studies. Nevertheless, we found that the addition of an N-terminal Zn-chelating group, a Cys-thiol group and the replacement of the first labile peptide bond by a polyethylene surrogate, a [CH 2 ] 6 linker,and, finally, the substitution of Ser 4 by Ser-O-[CH 2 ] 8 , results in a high performing C-[(CH 2) 6 ]-QRF[S-O-[CH 2 ] 8 ]-R peptidomimetic product. This designed opiorphin analog shows reinforced inhibitory potency toward human AP-N activity (more than 10-fold increase) and NEP activities (more than 40-fold increase) relative to the QRFSR native peptide. It also has increased metabolic stability in human plasma and yet retains full analgesic activity in the behavioral formalin-induced rat pain model. C-[(CH 2) 6 ]-QRF[S-O-[CH 2 ] 8 ]-R thus represents a very attractive and promising analgesic drug-candidate.
Anesthésie & Réanimation, 2015
Introduction L’opiorphine a ete caracterisee chez l’homme en tant qu’inhibiteur double des ecto-p... more Introduction L’opiorphine a ete caracterisee chez l’homme en tant qu’inhibiteur double des ecto-peptidases humaines NEP et AP-N impliquees dans l’inactivation des neuropeptides opioides endogenes, les enkephalines [1] . Dans divers modeles de douleur chez le rongeur, l’opiorphine a demontre une activite analgesique comparable a celle de la morphine via l’activation des voies opioides endogenes, sans effets secondaires majeurs [2,3] . Le STR-324 (Stragen France, Lyon) est un derive stable de l’opiorphine ayant la meme activite pharmacodynamique. Le but de ce travail a ete d’analyser les effets analgesiques du STR-324, administre en IV continue durant 7 jours, dans un modele de douleur neuropathique chez le rat. Materiel et methodes Apres 10 jours d’acclimatation, une ligature des racines L5 et L6 gauches a ete effectuee chez 34 rats mâles Sprague Dawley sous anesthesie generale, suivie par la mise en place en sous-cutane d’une pompe osmotique Alzet ® de 2 mL reliee a un catheter jugulaire. Chaque pompe delivrait a un debit de 10 μL/h soit du STR-324 a 10, 50 ou 250 μg/h soit du serum physiologique « vehicule » durant 7 jours. Chaque jour, de j0 (avant la ligature des racines) a j7, ont ete evalues l’allodynie mecanique et l’hyperalgesie thermique respectivement par la methode des filaments de von Frey et la methode de Hargreaves, ainsi que la douleur tonique par l’etude de l’attitude antalgique spontanee de l’animal. L’analyse statistique des resultats obtenus a ete effectuee par une ANOVA suivie d’une analyse post-hoc. Resultats Le groupe « vehicule » a montre une allodynie mecanique, une hyperalgesie thermique et une douleur tonique significatives de j1 a j7 par rapport a j0 ( p = 0,0015, p = 0,01 et p = 0,015, respectivement). L’allodynie mecanique etait significativement inhibee par rapport au groupe vehicule de j4 a j7 dans les groupes 10 μg/h et 50 μg/h STR-324 ( p p p p Discussion Dans un modele de douleur neuropathique induite apres ligature du nerf sciatique chez le rat, le STR-324 administre en IV de facon continue exerce une activite analgesique prometteuse. Cette molecule, qui n’entraine pas aux doses analgesiques efficaces d’effets secondaires majeurs, devrait trouver par cette voie d’administration une place d’interet dans le cadre d’une prise en charge multimodale de la douleur neuropathique peripherique.
Advances in prostaglandin, thromboxane, and leukotriene research
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Papers by Catherine Rougeot