Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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48 Studies on CHO-hAT1 cells will involve radioligand binding experiments with [ 3H]angiotensin II to investigate the amount of internalised receptors as a function of the incubation time and the agonist concentration. In these experiments, expertise from previous work will be used to discriminate the binding to cell surface and internalised receptors (Fierens et al 2000b). Following the pre-treatment of the cells with unlabelled angiotensin II, it is possible to monitor the reappearance of recycled AT 1 receptors at the cell surface by binding studies with [ 3H]candesartan (which associates very fast at 5 nM, Vanderheyden et al., 2000a). Similar experiments involving a double preincubation step (the first one with angiotensin II to induce receptor internalisation and the second one with antagonist) will provide information about the effect of agonist exposure on the extent and duration of antagonist action. For these experiments, it is not possible to monitor the recovery of receptors by measuring the IP production because of its cumulative nature (due to the presence of LiCl in the assay medium). Yet, human cell lines expressing AT 1 receptors allow the measurement of more distant functional responses and, hence, to circumvent the technical limitations that are inherent to IP measurements. Obviously, it is of interest to explore whether the angiotensin II- mediated internalisation/ desensitisation of AT 1 receptors and its potential effect on antagonist action is cell dependent or not. In this respect, we will also have the opportunity to compare data from our intact cell experiments with those of related contraction studies on rat portal vein by Dr. P. Morsing and co-workers (unpublished observations).
References •Aiyar N, Baker E, Vickery-Clark L, Ohlstein EH, Gellai M, Fredrickson TA, Brooks DP et al.: Pharmacology of a potent long-acting imidazole-5-acrylic acid angiotensin AT1 receptor antagonist. Eur J Pharmacol 283: 63-72, 1995. •Anderson KM, Murahashi T, Dorstal DE and Peach MJ: Morphological and biochemical analysis of angiotensin II internalization in cultured rat aortic smooth muscle cells. Am J Physiol 264: C179-C188, 1993. • Berk BC: Angiotensin II Signal Transduction in Vascular Smooth Muscle: Pathways Activated by Specific Tyrosine Kinases. J Am Soc Nephrol, 10: S62-S68, 1999. •Bumpus FM, Catt KJ, Chiu AT, DeGasparo M, Goodfriend T, Husain A, Peach M., Taylor DG Jr. and Timmermans PB: Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research. Hypertension 17: 720-721, 1991. • Cazaubon C, Gougat J, Bousquet F, Guiraudou P, Gayraud R, Lacour C, Roccon A et al.: Pharmacological characterization of SR 47436, a new non-peptide ATl subtype angiotensin II receptor antagonist. J Pharmacol Exp Ther 265: 826-834, 1993. •Cirillo R, Renzetti AR, Cucchi P, Guelfi M, Salimbeni A, Caliari S, Castellucci A et al.: Pharmacology of LR-B/081, a new highly potent, selective and orally active, nonpeptide angiotensin II AT1 receptor antagonist. Br J Pharmacol 114: 1117-1124, 1995. •Criscione L, de Gasparo M, Bühlmayer P, Whitebread S, Ramjoué HP and Wood J: Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1 receptor subtype. Br J Pharmacol 110: 761-771, 1993. •De Arriba AF, Gomez-Casajus LA, Cavalcanti F, Almansa C, Garcia-Rafanel J and Forn J: In vitro pharmacological characterization of a new selective angiotensin AT1 receptor antagonist, UR-7280. Eur J Pharmacol 318: 341-347, 1996. • de Chaffoy de Courcelles D, Leysen JE, Roevens P and Van Belle H: The serotonin-S2 receptor: A receptor, transducer coupling model to explain insurmountable antagonist effects. Drug Development Research 8: 173-178,1986. •Dickinson KE, Cohen RB, Skwish S, Delaney CL, Serafino RP, Poss MA, Gu Z et al.: BMS- 180560, an insurmountable inhibitor of angiotensin II- stimulated responses: comparison with losartan and EXP3174. Br J Pharmacol 113: 179-189, 1994. •Fierens FLP, Vanderheyden PML, De Backer J-P and Vauquelin G: Binding of the antagonist [ 3H]candesartan to angiotensin II AT1 receptor- transfected Chinese hamster ovary cells. Eur J Pharmacol 367: 413-422, 1999a. •Fierens F, Vanderheyden P, De Backer J-P and Vauquelin G: Insurmountable angiotensin II AT1 receptor antagonists: the role of tight antagonist binding. Eur J Pharmacol 372: 199- 206, 1999b. •Fierens FLP, Vanderheyden PML, Gaborik Z, Le Minh T, J-P DeBacker, Hunyady L, Ijzerman A and Vauquelin G: Lys 199 Mutation of the human angiotensin II AT1 receptor differently affects the binding of surmountable and insurmountable non-peptide antagonists. J Renin- Angiotensin-Aldosterone Syst (2000a, in press) 49
Page 1 and 2: Geneeskundige Stichting Koningin El
Page 3 and 4: Fondation Médicale Reine Elisabeth
Page 5 and 6: L’abondance et la qualité des pu
Page 7 and 8: Prof. Dr. A. Bossuyt Secrétaire du
Page 9 and 10: Prof. Dr. G. Orban Lab. voor Neuro-
Page 11: Reports of the University Research
Page 14 and 15: 14 Members of the team: Christophe
Page 16 and 17: 16 domains, most notably that of N-
Page 19 and 20: Report of the Research Group of Pro
Page 21 and 22: Part 1: Characterisation of noradre
Page 23 and 24: Part 2 : Chromogranins as neuro-imm
Page 25: Publications 2000 : • J. Depreite
Page 28 and 29: 28 Collaborations with: A. Volny-Lu
Page 30 and 31: 30 MATERIALS AND METHODS Surgery an
Page 32 and 33: 32 RESULTS Recordings were obtained
Page 34 and 35: 34 Responses to brush stimuli The s
Page 36 and 37: 36 DISCUSSION This experimental stu
Page 41 and 42: PART 1: Molecular Pharmacology of A
Page 43 and 44: c) Most insurmountable AT 1 recepto
Page 45 and 46: dy tested biphenyl-tetrazole derive
Page 47: ii) More distant functional respons
Page 51 and 52: •Olins GM, Chen ST, McMahon EG, P
Page 53 and 54: PART 2: The use of Endothelin 1 in
Page 55 and 56: vasoconstriction, peaked 20 minutes
Page 57: ACCEPTED • Vanderheyden P.M.L., F
Page 60 and 61: 60 Prof. Dr. Christophe Erneux I.R.
Page 62 and 63: 62 tion forming Ins(1,3,4,5)P 4 and
Page 64: 64 Bibliography •Berridge, M.J. a
Page 68 and 69: 68 University of Mons-Hainaut Labor
Page 70 and 71: 70 Works carried out in 2000 1. We
Page 75 and 76: Genetic definition of brain tumours
Page 77 and 78: Analysing this way these 48 tumours
Page 83 and 84: Genetic determinants of mouse brain
Page 85 and 86: Genomic organization of the Dab1 ge
Page 91 and 92: In vitro studies of the hypothalami
Page 93 and 94: vitro GnRH release by intact male g
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Study on the functional regulation
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Elucidation of the DAT primary sequ
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The role of presenilin-1 in the gam
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Report of the Research Group of Pro
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INTRODUCTION As usual, this activit
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The acquisitions for this study sho
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not lead to the integrative process
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REFERENCES Thesis •Steven Laureys
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• Positron emission tomography in
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Before scanning, subjects practised
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RESEARCH PROGRAM ON MEMORY FUNCTION
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Corticobasal degeneration, motor sl
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Figure 2. Brain Areas Disclosed Dur
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• Cognitive Neuropsychological an
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Neuregulin signaling regulates neur
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tein present in neural precursor ce
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Cell biology for prevention and tre
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Functional significance of neurorec
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Spinal Cord Traumatic Lesion Martin
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A.Schulman, and T.R.Van De Water, B
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•Identification of PSF, the PTB-a
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143
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Brain activations in a dot pattern
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References •R Vogels, G Sary, P D
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A Scientific activities 1. Overview
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4. Purinergic receptors. Purinergic
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mals also scored higher in anxiety
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cell clones have been used in these
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•Ledent C, Valverde O, Cossu G, P
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• Snell BJ, Short JL, Drago J, Le
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I. Physiology and physiopathology o
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nuclei, which are involved in respo
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Natl. Acad. Sci. USA, 96: 5257-5262
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in those who did not. In rats sacri
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(Poster). Abstract of the 4th EURON
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Positional cloning of the neuronal
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fragments, 18 expressed-sequence-ta
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Philadelphia, USA, 3-7 October 2000
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I. FMRI in Awake Behaving Macaques
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gressively higher levels of the cor
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MION was injected into the femoral
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Future Possibilities Future contras
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FIGURES Figure 1: FMRI responses in
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Figure 5: Average percent signal ch
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FUNCTIONAL MAGNETIC RESONANCE IMAGI
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explain these search processes. Par
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205
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Investigation of the molecular mech
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tral) cortex compared to non-depriv
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By comparing the percentual increas
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altered amino acid residue is equal
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BIBLIOGRAPHY - 2000 Publications in
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Soc. Neurosci. Abstr., 2000, vol. 2
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1. Coding of 3D-shape in macaque in
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3. Position sensitivity of macaque
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Publications: •JANSSEN P., VOGELS
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