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Neuropeptide receptor expression in inflammatory bowel disease

Beek, W.P. ter

Citation

Beek, W. P. ter. (2008, April 3). Neuropeptide receptor expression in inflammatory bowel disease. Retrieved from https://hdl.handle.net/1887/12667

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/12667

Note: To cite this publication please use the final published version (if applicable).

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Neuropeptide Receptor Expression in

Inflammatory Bowel Disease

Pascale ter Beek

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ISBN: 978-90-9022832-7

Printed by Gildeprint Drukkerijen B.V., Enschede, The Netherlands

© W.P. ter Beek, Leiden 2008

No part of this publication may be reproduced, stored in retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, and recording or otherwise, without prior written permission of the author.

The work described in this thesis was performed at the Department of Gastroenterology and

Hepatology of the Leiden University Medical Center (Leiden, The Netherlands). The project was partly financed by a grant from the Netherlands Digestive Diseases Foundation (WS 97-23).

Printing of this thesis was financially supported by the Section Experimental Gastroenterology (SEG) of the Netherlands Society of Gastroenterology (NVGE).

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Neuropeptide Receptor Expression in

Inflammatory Bowel Disease

PROEFSCHRIFT

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. P.F. van der Heijden,

volgens besluit van het College voor Promoties te verdedigen op donderdag 3 april 2008

Klokke 16.15 uur

door

Willy Pascale ter Beek geboren te Almelo

in 1974

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Promotiecommissie

Promotor: Prof. dr. C.B.H.W. Lamers

Co-promotor: Dr. ir. I. Biemond

Referent: Prof. dr. J.B.M.J. Jansen, Universitair Medisch Centrum St. Radboud, Nijmegen

Overige leden: Prof. dr. A.A.M. Masclee, Universiteit Maastricht

Prof. dr. G.J.A. Offerhaus, Universitair Medisch Centrum Utrecht Prof. dr. H. Morreau

Dr. ir. H.W. Verspaget

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Contents

Abbreviations 7

Chapter one Introduction 9

Chapter two Outline and aims of this thesis 37

Chapter three Substance P receptor expression in patients with inflammatory bowel disease

41

Chapter four Quantification of neurotensin binding sites at different locations in inflammatory bowel disease and control human intestine

55

Chapter five Identification of neurotensin binding sites: Neurotensin receptor-1 and -3 are expressed in the human

gastrointestinal tract

69

Chapter six Gastrin-releasing peptide receptor expression is decreased in Crohn's disease but not in ulcerative colitis

85

Chapter seven Motilin receptor expression in smooth muscle, myenteric plexus and mucosa of human inflamed and noninflamed intestine

101

Chapter eight Summarizing discussion 119

Chapter nine Samenvatting 129

Nawoord 141

Curriculum Vitae 143

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Abbreviations - 7

Abbreviations

5-HT Serotonin

Ach Acetylcholine

ATP Adenosine triphosphate

BN Bombesin

BRS Bombesin receptor subtype BSA Bovine serum albumin

CD Crohn’s disease

cDNA complementary desoxyribonucleic acid ENS Enteric nervous system

GALT Gut-associated lymphoid tissue GPR38-A G-protein coupled receptor 38-A GRP Gastrin-releasing peptide H2O2 Hydrogen peroxidase IBD Inflammatory bowel disease

IL Interleukin

Kd Dissociation constant

MPO Myeloperoxidase

mRNA Messenger ribonucleic acid

NK Neurokinin

NMB Neuromedin B

NRS Normal rat serum

NT(R) Neurotensin (receptor)

RT-PCR Reverse-transcriptase polymerase chain reaction SEM Standard error of the mean

SP Substance P

TBS Tris-buffered saline

TNBS Trinitrobenzenesulfonic acid UC Ulcerative colitis

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