Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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98 Professeur Jean-Marie Maloteaux Laboratoire de Pharmacologie Université Catholique de Louvain UCL 54. 10 Avenue Hippocrate, 54 - 1200 Bruxelles Tel.: +32.2.764.54.37 - Fax: +32.2.764.93.36 Collaborator Prof. Dr. J.N. Octave Prof. Dr. E. Hermans
Study on the functional regulation of the neurotransmission During year 2000, two different projects have benefit from the financial support of the <strong>FMRE</strong> : Characterization of the functional coupling of the neurotensin receptor with muplitple G-proteins • Evidence for the dual coupling of the rat neurotensin receptor with pertussis toxin-sensitive and insensitive Gproteins. Gailly P., Najimi M. & Hermans E. (2000) FEBS Lett., 483, 109-113. • Interaction with Gαi and Gαq protein subunits promotes high affinity agonist binding to the neurotensin receptor NTS-1 expressed in E.Coli.’ Hermans E. & Grisshammer R. submitted to Biochem. J. The effects of the neuropeptide neurotensin (NT) are thought to result from its high affinity interaction with specific membrane receptors. Early binding studies conducted on brain tissues and cell lines led many authors to propose the existence of multiple NT binding sites. Three NT receptor subtypes have now been cloned and named NTS1, nts2 and nts3. NTS1 and nts2 belong the large family of G-protein coupled receptors whereas nts3 corresponds to the previously characterized gp95/sortilin containing a single transmembrane domain. In contrast to nts2 and nts3, that were only clearly identified in the late 90ies, NTS1 has received much more attention and was extensively studied in a large variety of cell lines, tissues and recombinant systems for more than a decade. The coupling of this receptor with G-proteins is demonstrated by the ability of guanylyl nucleotides and Na + ions to modulate the binding affinity of NT agonists. Although both positive and negative controls of adenylyl cyclase by NT were reported in some cultured cells expressing NTS1, most of the effects of NT have been attributed to the activation of PLC. This suggests the involvement of G q/11-type G-proteins and accordingly, many responses to NT are unaffected by the inactivation of G i/o-type G-proteins by PTx or N-ethylmaleimide. However, this is not the rule and a number of authors have also proposed a possible coupling of NT receptors with other signaling pathways that are proposed to involve PTxsensitive G-proteins. Using transfected CHO cells expressing NTS1 (CHO-NTR), we previously demonstrated the functional coupling of the rat neurotensin receptor NTS1 with G-proteins on transfected CHO cell homogenates by showing modulation of agonist affinity by guanylyl nucleotides and agonist mediated stimulation of [ 35S]-GTPγS binding. In the present study, we observed that G i/o-type G-protein inactivation by pertussis toxin (PTx) resulted in a dramatic reduction of the NT-induced [ 35S]-GTPγS binding whereas the effect of guanylyl nucleotide was almost not affected. As expected, NT-mediated phosphoinositides hydrolysis and intracellular calcium mobilization were not altered after PTx treatment. This suggests the existence of multiple signaling cascades activated by NT. Accordingly, using PTx and the PLC inhibitor U-73122 we showed that both signaling pathways contribute to the NT-mediated production of arachidonic acid. These results support evidence for a dual coupling of the NTS1 with PTx-sensitive and insensitive G-proteins. Simultaneous coupling of membrane receptor with different G-proteins has frequently been reported, especially when using recombinant models in which high levels of receptor expression may facilitate the detection of either promiscuous or specific but low-efficient coupling. A variety of responses induced by NT in vivo were shown to be dependent on 99
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Geneeskundige Stichting Koningin El
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Fondation Médicale Reine Elisabeth
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L’abondance et la qualité des pu
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Prof. Dr. A. Bossuyt Secrétaire du
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Prof. Dr. G. Orban Lab. voor Neuro-
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Reports of the University Research
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14 Members of the team: Christophe
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16 domains, most notably that of N-
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Report of the Research Group of Pro
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Part 1: Characterisation of noradre
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Part 2 : Chromogranins as neuro-imm
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Publications 2000 : • J. Depreite
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28 Collaborations with: A. Volny-Lu
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30 MATERIALS AND METHODS Surgery an
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32 RESULTS Recordings were obtained
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34 Responses to brush stimuli The s
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36 DISCUSSION This experimental stu
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PART 1: Molecular Pharmacology of A
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c) Most insurmountable AT 1 recepto
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dy tested biphenyl-tetrazole derive
Page 47 and 48: ii) More distant functional respons
Page 49 and 50: References •Aiyar N, Baker E, Vic
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 73 and 74: Report of the Research Group of Pro
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
Page 97: Report of the Research Group of Pro
Page 101 and 102: Elucidation of the DAT primary sequ
Page 103 and 104: The role of presenilin-1 in the gam
Page 107 and 108: INTRODUCTION As usual, this activit
Page 109 and 110: The acquisitions for this study sho
Page 111 and 112: not lead to the integrative process
Page 113 and 114: REFERENCES Thesis •Steven Laureys
Page 115 and 116: • Positron emission tomography in
Page 117 and 118: Before scanning, subjects practised
Page 119 and 120: RESEARCH PROGRAM ON MEMORY FUNCTION
Page 121 and 122: Corticobasal degeneration, motor sl
Page 123 and 124: Figure 2. Brain Areas Disclosed Dur
Page 125 and 126: • Cognitive Neuropsychological an
Page 129 and 130: Neuregulin signaling regulates neur
Page 131 and 132: tein present in neural precursor ce
Page 133 and 134: Cell biology for prevention and tre
Page 135 and 136: Functional significance of neurorec
Page 137 and 138: Spinal Cord Traumatic Lesion Martin
Page 139 and 140: A.Schulman, and T.R.Van De Water, B
Page 141 and 142: •Identification of PSF, the PTB-a
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Page 147 and 148: 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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Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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