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Immunohistochemical Detection of Gastrin and Motilin Peptides, Their Receptors, VIP Receptors and Caspase Activity from the Abomasal Wall of Cattle

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Immunohistochemical Detection of Gastrin and Motilin Peptides, Their Receptors, VIP Receptors and Caspase Activity from the Abomasal Wall of Cattle Immunohistochemical detection of gastrin and motilin peptides, their receptors, VIP receptors and caspase activity from the abomasal wall of cattle AYCAN ÖZCAN DETECTION OF PEPTIDES FROM ABOMASAL WALL édition scientifique VVB LAUFERSWEILER VERLAG INAUGURAL-DISSERTATION zur Erlangung des Grades eines Dr. med. vet. VVB LAUFERSWEILER VERLAG beim Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen STAUFENBERGRING 15 ISBN: 978-3-8359-5914-9 D-35396 GIESSEN AYCAN ÖZCAN Tel: 0641-5599888 Fax: -5599890 [email protected] www.doktorverlag.de 9 783835 959149 édition scientifique VVB LAUFERSWEILER VERLAG VVB Das Werk ist in allen seinen Teilen urheberrechtlich geschützt. Jede Verwertung ist ohne schriftliche Zustimmung des Autors oder des Verlages unzulässig. Das gilt insbesondere für Vervielfältigungen, Übersetzungen, Mikroverfilmungen und die Einspeicherung in und Verarbeitung durch elektronische Systeme. 1. Auflage 2012 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the Author or the Publishers. 1st Edition 2012 © 2012 by VVB LAUFERSWEILER VERLAG, Giessen Printed in Germany VVB LAUFERSWEILERédition scientifique VERLAG STAUFENBERGRING 15, D-35396 GIESSEN Tel: 0641-5599888 Fax: 0641-5599890 email: [email protected] www.doktorverlag.de Aus dem Klinikum Veterinärmedizin, Klinik für Wiederkäuer und Schweine (Innere Medizin und Chirurgie) und dem Institut für Veterinär-Anatomie, -Histologie und -Embryologie der Justus-Liebig-Universität Gießen Betreuer: Prof. Dr. Dr. habil. K. Doll Prof. Dr. Dr. S. Arnhold Immunohistochemical detection of gastrin and motilin peptides, their receptors, VIP receptors and caspase activity from the abomasal wall of cattle INAUGURAL–DISSERTATION zur Erlangung des Grades eines Dr. med. vet. beim Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen eingereicht von Aycan Özcan Tierarzt aus Meric (Türkei) Giessen 2012 Mit Genehmigung des Fachbereichs Veterinärmedizin der Justus-Liebig-Universität Gießen Dekan: Prof. Dr. Dr. h. c. M. Kramer Gutachter: Prof. Dr. Dr. habil. K. Doll Prof. Dr. Dr. S. Arnhold Tag der Disputation: 25. Juni 2012 Dedicated to my family Anne ve Babama Parts of this study have been presented in the following conferences: A. Özcan, M. Sickinger, S. Arnhold, K. Doll (2011): Zur ätiopathogenetischen Bedeutung von Neurotransmittern bei der Labmagenverlagerung der Milchkuh. Oral presentation, 8th buiatrics conference, 1-3.4.2011, Oberschleißheim M. Sickinger, A. Özcan, R. Leiser, S. Arnhold, K. Doll (2011): Neuropeptidgehalte und Innervationsdichte in der Labmagenwand von Holstein-Kühen. Ätiopathogenetische Bedeutung hinsichlich Labmagenverlagerung? Proceedings, 3rd annual conference of German Buiatrics Association DVG, 10-13.11.2011, Berlin, 90-92 Table of contents Table of abbreviations ........................................................................................ 3 Index of figures .................................................................................................... 5 Index of tables ...................................................................................................... 7 1 Introduction and aims of the study ................................................................. 8 2 Literature review ............................................................................................ 11 2.1 Innervation of the gastrointestinal tract .......................................................................... 11 2.1.1 Extrinsic nervous system ......................................................................................... 12 2.1.1.1 Parasympathetic nerves ........................................................................................ 12 2.1.1.2 Sympathetic nerves .............................................................................................. 12 2.1.2 Enteric nervous system............................................................................................ 12 2.2 Neuropeptides and gastrointestinal hormones ................................................................ 13 2.3 Gastrointestinal peptides ................................................................................................ 14 2.3.1 Gastrin ..................................................................................................................... 14 2.3.2 Motilin ..................................................................................................................... 19 2.3.3 Vasoactive intestinal polypeptide ............................................................................ 23 2.4 Caspases ......................................................................................................................... 27 3 Materials and methods ................................................................................... 30 3.1 Tissue material ............................................................................................................... 30 3.2 Fixation of the samples .................................................................................................. 31 3.3 Immunohistochemistry ................................................................................................... 31 3.4 Antibodies and controls .................................................................................................. 32 3.5 Immunohistochemical staining protocols for the peptides, receptors and caspase activity ............................................................................................................................ 37 3.6 Microscopic examination and digital imaging ............................................................... 45 3.7 Measurement of the immunoreactive staining ............................................................... 45 4 Statistical analysis .......................................................................................... 46 5 Results .............................................................................................................. 47 5.1 Results of gastrin immunoreactivity .............................................................................. 47 5.2 Results of gastrin/CCKB receptor immunoreactivity .................................................... 50 5.3 Results of motilin immunoreactivity .............................................................................. 52 5.4 Results of motilin receptor immunoreactivity ................................................................ 53 5.5 Results of VPAC2 .......................................................................................................... 57 5.6 Results of VPAC1 .......................................................................................................... 58 5.7 Results of caspase activity .............................................................................................. 61 5.8 Results of the experimentally induced abomasal dilatation ........................................... 65 5.8.1 Results from the first operation, before the application of a gastric band .............. 65 5.8.2 Results from the second operation, after the application of a gastric band ............. 67 5.8.3 Comparison of the results between the healthy German Holstein cows without an abomasal displacement and the experimentally induced abomasal impaction group before placing a gastric band ....................................................... 71 5.8.4 Comparison of the results between the German Holstein cows with abomasal displacement and the experimentally induced abomasal impaction group after placing a gastric band ............................................................................................. 75 5.9 Relationship between the receptors and caspase activity ............................................... 78 5.9.1 Relationship between caspase activity and motilin receptor ................................... 79 5.9.2 Relationship between caspase activity and VPAC1/VIP-1 receptor ....................... 80 5.9.3 Relationship between VPAC1/VIP-1 receptor and motilin receptor ...................... 81 1 6 Discussion ........................................................................................................ 82 6.1 Discussion of the immunohistochemical ABC method ................................................. 82 6.2 Discussion of immunohistochemical staining results .................................................... 84 6.3 Conclusions .................................................................................................................... 92 7 Summary ......................................................................................................... 93 8 Zusammenfassung .......................................................................................... 96 Bibliography ....................................................................................................... 99 Appendices ....................................................................................................... 127 2 Table of abbreviations ABC Avidin-Biotin-Complex ACh Acetylcholin AD Abomasal displacement AEC 3-Amino-9-ethylcarbazol AIF Apoptosis inducing factor Apaf 1 Apoptosis protease activating factor 1 Blc-2 B-cell lymphoma 2 BSA Bovine serum albumin Ca²+ Calcium cAMP Cyclic adenosine
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