PHYSIOLOGICAL AND PHARMACOLOGICAL ASPECTS OF THE RETICULO-RUMEN CURRENT TOPICS IN VETERINARY MEDICINE AND ANIMAL SCIENCE Control of Reproduction in the Cow, The Elisa: Enzyme-Linked edited by 1.M. Sreenan lmmunosorbent Assay in Veterinary Research and Diagnosis, edited by R.C. Wardley and 1.R. Patterns of Growth and Development in Crowther Cattle, edited by H. de Boer and 1. Martin Indicators Relevant to Farm Animal Respiratory Diseases in Cattle, edited by Welfare, edited by D. Smidt W.B. Martin Farm Animal Housing and Welfare, Calving Problems and Early Viability of edited by S.H. Baxter, M.R. Baxter and 1.A.D. the Calf, edited by B. Hoffmann, 1.L. Mason and 1. MacCormack Schmidt Stunning of Animals for Slaughter, edited The Future of Beef Production in the by G. Eikelenboom European Community, edited by J.c. Bowman and P. Susmel Manipulation of Growth in Farm Animals, edited by 1.F. Roche and D. O'Callaghan Diseases of Cattle in the Tropics: Economic and Zoonotic Relevance, edited by M. Latent Herpes Virus Infections in Ristic and I. McIntyre Veterinary Medicine, edited by G. Wittmann, R.M. Gaskell and H .-1. Rziha Control of Reproductive Functions in Domestic Animals, edited by W. lochle and D.R. Grassland Beef Production, edited by W. Lamond Holmes The Laying Hen and its Environment, Recent Advances in Virus Diagnosis, edited by R. Moss edited by M.S. McNulty and 1.B. McFerran Epidemiology and Control of The Male in Farm Animal Reproduction, Nematodiasis in Cattle, edited by P. Nansen, R.l. edited by M .Courot 10rgensen and E.l.L. Soulsby Endocrine Causes of Seasonal and The Problem of Dark-Cutting in Beef, Lactational Anestrus in Farm Animals, edited by F. edited by D.E. Hood and P.V. Tarrant Ellendorff and F. Elsaesser The Welfare of Pigs, edited by Brucella Melitensis, edited by 1.M. Verger W. Sybesma and M. Plommet The Mucosal Immune System, edited by Diagnosis of Mycotoxicoses, edited by F.l. Bourne 1.L. Richard and 1.R. Thurston Laboratory Diagnosis in Neonatal Calf Embryonic Mortality in Farm Animals, and Pig Diarrhoea, edited by P. W. de Leeuw and edited by J.M. Sreenan and M.G. Diskin P.A.M. Guinee Social Space for Domestic Animals, edited Advances in the Control of Theileriosis, by R. Zayan edited by A.D. Irvin, M.P. Cunningham and A.S. The Present State of Leptospirosis Young Diagnosis and Control, edited by W.A. Ellis and Fourth International Symposium on T.W.A. Little Bovine Leukosis, edited by O.c. Straub Acute virus infections of poultry, edited Muscle Hypertrophy of Genetic Origin by 1.B. McFerran and M.S. McNulty and its Use to Improve Beef Production, edited by Evaluation and Control of Meat Quality 1. W. B. King and F. Menissier in Pigs, edited by P.V. Tarrant, G. Eikelenboom and Aujeszky's Disease, edited by G. Wittman G. Monin and S.A. Hall Follicular Growth and Ovulation Rate in Transport of Animals Intended for farm Animals, edited by 1.F. Roche and D. Breeding, Production and Slaughter, edited by R. O'Callaghan Moss Cattle Housing Systems, Lameness and Welfare and Husbandry of Calves, edited Behaviour, edited by H.K. Wierenga and D.l. Peterse by 1. P. Signoret Physiological and Pharmacological Factors Influencing Fertility in the Aspects of the Reticula-Rumen, edited by L.A.A. Postpartum Cow, edited by H. Karg and Ooms, A.D. Degryse and A.S.J.P.A.M. van Miert E. Schallenberger Beef Production from Different Dairy Breeds and Dairy Beef Crosses, edited by G.l. More O'Ferrall PHYSIOLOGICAL AND PHARMACOLOGICAL ASPECTS OF THE RETICULO-RUMEN Edited by L.A.A. Ooms and A.D. Degryse Department oj Veterinary Pharmacology, Janssen Pharmaceutica, Beerse, Belgium A.S.J.P.A.M. van Miert Department oj Veterinary Pharmacology, Pharmacy and Toxicology, Faculty oj Veterinary Medicine, Utrecht University, Utrecht, The Netherlands 1987 MARTINUS NIJHOFF PUBLISHERS a member of the KLUWER ACADEMIC PUBLISHERS GROUP DORDRECHT / BOSTON / LANCASTER Distributors for the United States and Canada: Kluwer Academic Publishers, P.O. Box 358, Accord Station, Hingham, MA 02018-0358, USA for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LAl lRN, UK for all other countries: Kluwer Academic Publishers Group, Distribution Center, P.O. Box 322, 3300 AH Dordrecht, The Netherlands Library of Congress Cataloging in Publication Data ISBN-13:978-94-010-7990-7 e-ISBN-13: 978-94-009-3319-4 001: 10.1007/978-94-009-3319-4 Copyright © 1987 by Martinus Nijhoff Publishers, Dordrecht. Softcover reprint of the hardcover 1st edition 1987 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, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publishers, Martinus Nijhoff Publishers, P.O. Box 163, 3300 AD Dordrecht, The Netherlands. v PREFACE The success of a scientific workshop depends on a delicate blend of many types of ingredients. Most important is to select a provocative topic which is at the forefront of a current investigative study. Coupled together with a relatively small but distinguished group of active research scientists known for their continued record of contributing significant findings, one has the firm foundation for an exciting and rewarding investment of time and effort. This was the setting for the first workshop organized by the European Association for Veterinary Pharmacology and Toxicology. Ruminants have been domesticated for many centuries and have served mankind as a source of dairy products, meat, wool and power. The ruminant stomach has long been - and still is - a major concern for physiologists, pathologists, clinicians and pharmacologists. This workshop was organized and convened in an attempt to strengthen the basic science of the ruminant stomach, as it applies to an economically important group of mammals. To achieve this, various topics were covered by specialists which ensured presentation of new data, followed by discussions. In this book, reviews are presented on the different topics: motility (control and regulation, neurotransmitters and endogenous substances involved); flow of digesta (comparative aspects, role of content and metabolites); food intake; rumen metabolism (chemical manipulation, metabolism of xenobiotics and drugs); pharmacology of forestomach motility and, the reticulo-rumen as a pharmacokinetic compartment. This book is dedicated to Dr. Paul Janssen, President and Director of Research of Janssen Pharmaceutica, on the occasion of his 60th birthday. The editors would like to thank Dr. Robert Marsboom, Vice President and Head of the Veterinary Department of Janssen Pharmaceutica, for the facilities to organize the workshop. The co-editors (L.O. and A.-D.D.) also wish to thank Mrs. C.W.P. Stigter- van Vliet from the Department of Veterinary Physiology (Utrecht) and Mr. J.M. Eijndhoven from the Department of Veterinary Pharmacology, Pharmacy and Toxicology (Utrecht) for technical assistance in preparing the manuscripts as well as Prof. Dr. A.S.J.P.AJM. van Miert for his encouragement and preparation of the book. VII CONTENTS Preface and Acknowledgements v List of Contributors IX Chapters 1. The control of the motility of the reticulo-rumen. B.F. Leek 2. Reticulo-rumen and gastroduodenal junction motility. Y. Ruckebusch 21 3. Neurotransmitters/neuromodulators involved in the motor and secretory functions of the ruminant stomach: a histochemical, radioimmunological, immunocytochemical and functional approach. A. Weyns, L.A.A. Ooms, A. Verhofstad, Th. Peeters, A.D. Degryse, L. van Nassauw and P. Krediet 43 4. Reticulo-rumen motility: in vitro and in vivo effects of endogenous substances. A.S.J.P.A.M. van Miert 113 5. Forestomach: control of digesta flow. A.G. Deswysen 133 6. Comparative studies of food propulsion in ruminants. R.N.B. Kay 155 7. Metabolic and endocrine controls of food intake in ruminants. A. de Jong 171 8. Rumen microbial metabolism of plant secondary compounds, xenobiotics and drugs. R.A. Prins 199 9. Chemical manipulation of rumen metabolism. D.I. Demeyer and C.J. van Nevel 227 10. The rumen as a pharmacokinetic compartment. J.A. Bogan and S.E. Marriner 253 11. Drug-induced effects on reticular groove reflex, eructation and rumination. L.A.A. Ooms, A.D. Degryse, A. Weyns, S. Bouisset and Y. Ruckebusch 271 Index of subjects 307 IX LIST OF CONTRIBUTORS J.A. BOGAN R.N.B. KAY Department of Veterinary Rowett Research Institute Pharmacology Greenburn Road, Bucksburn University of Glasgow Aberdeen AB2 9SB Veterinary School Scotland Bearsden Road, Bearsden Glasgow GGI IQH Scotland P. KREDIET Department of Veterinary Anatomy and Embryology S. BOUISSET Faculty of Sciences Docteur Veterinaire University of Antwerp 5 Route de Challans Slachthuislaan 68 85190 Aizenay B-2000 Antwerp France Belgium A.D. DEGRYSE B.F. LEEK Department of Veterinary Department of Veterinary Physiology Pharmacology and Biochemistry Janssen Pharmaceutica University College Dublin B-2340 Beerse Veterinary College, Ballsbridge Belgium Dubl in 4 Ireland A. DE JONG S.E. MARRINER Institute for Chemotherapy Bayer A.G. Department of Veterinary Pharma- P.O. Box 101709 cology 5600 Wuppertal 1 University of Glasgow Federal Republic of Germany Veterinary School Bearsden Road, Bearsden Glasgow GGI IQH D.I. DEMEYER Scotland Institute of Biotechnology Free University of Brussels L.A.A. OOMS Paardenstraat 65 B-1640 St.-Genesius Rode Department of Veterinary Pharma- Belgium cology Janssen Pharmaceutica B-2340 Beerse A.G. DESWYSEN Belgium Nutritional Biochemistry Lab. Department of Applied Animal Biology TH. PEETERS Catholic University of Louvain-la-Neuve Sciences 15-D2-tour Kellner Gut Hormones Laboratory Place Croix du Sud, 3 Catholic University of Louvain B-1348 Louvain-la-Neuve Louvain Belgium Belgium x R.A. PRINS A. WEYNS Research Institute of Nature Management Department of Veterinary Anatomy P.O. Box 46 and Embryology 3956 ZR Leersum Faculty of Science The Netherlands University of Antwerp Slachthuislaan 68 Y. RUCKEBUSCH B-2000 Antwerp Department of Physiology and Pharmacology Belgium National Veterinary School 23, Chemin des Capelles 31076 Toulouse Cedex France A.S.J.P.A.M. van MIERT Department of Veterinary Pharmacology, Pharmacy and Toxicology Faculty of Veterinary Medicine University of Utrecht P.O. Box 80 176 3508 TO Utrecht The Netherlands L. van NASSAUW Department of Veterinary Anatomy and Embryology Faculty of Sciences University of Antwerp Slachthuislaan 68 B-2000 Antwerp Belgium C.J. van NEVEL Research Centre for Food, Animal Nutrition and Meat Technology Faculty of Sciences University of Ghent Proefhoevestraat 10 B-9230 Melle Belgium A. VERHOFSTAD Department of Anatomy and Embryology Catholic University of Nijmegen Nijmegen The Netherlands 1. THE CONTROL OF THE MOTILITY OF THE RETICULO- RUMEN B.F. LEEK Introduction II The intrinsic contractions of the reticulo-rumen III The extrinsic contractions of the reticulo-rumen 1. Efferent vagal nervous activity 2. Efferent splanchnic nervous activity 3. The gastric centres 4. Visceral sensory mechanisms 4.1. The effective stimuli 4.2. Visceral sensory receptors and their afferent pathways 4.2.1. Epithelial receptors 4.2.2. Tension receptors 4.2.3. Serosal receptors IV Conclusion I. INTRODUCTION In the absence of vagal and splanchnic nerves, the smooth muscle of the reticulo-ruminal walls undergoes low amplitude contractions ("intrinsic contractions"). The coordinated sequences of powerful contractions ("extrinsic contractions") constituting the 'primary' and 'secondary' cycle motility are dependent on bursts of efferent (motor) nerve impulses travelling in the vagal nerves. These bursts originate from the gastric centres located in the medulla oblongata of the hind-brain. The gastric centres do not appear to have a spontaneous rhythmicity but require an overall excitatory drive to be provided by inputs coming from other (mainly higher) parts of the central nervous system and from the periphery (mainly from the alimentary tract itself). Situations which have general effects on the central nervous system or 2 which alter conditions within the gut, particularly within the reticulo- -rumen, will therefore affect motility. II. THE INTRINSIC CONTRACTIONS OF THE RETICULO-RUMEN In the gut generally, two separate mechanisms exist for the production of intrinsic contractions. First, there are "intrinsic myogenic contractions" attributable to the rhythmic contractility of the muscle cells themselves and, secondly, there are "intrinsic neurogenic contractions" which require the involvement of the neurones of the myenteric plexus. Evidence exists for both kinds of intrinsic contractions in the reticulo-rumen. Leek (1,2) recorded reticulo-ruminal tension receptor activity by a 'single afferent vagel fibre' technique in halothane-anaesthetised sheep. In most cases, during the interval between extrinsic contractions, the tension receptors exhibited phasic discharges of spikes (action potentials) at a rate of about 10 cycles/min for the reticulum and 12 cycles/min for the cranial sac of the rumen. These rates were considered to be indicative of the respective rhythmicities of the intrinsic movements of these structures. Neither the phasic discharges of the tension receptors nor the frequency of efferent vagal discharges respon- sible for extrinsic contractions were affected by the administration of anti-cholinesteras~s (neostigmine), ganglionic blockers (tetraethyl- ammonium chloride) or muscarinic blockers (probanthine hydrochloride), even though, in contrast, the amplitudes of the extrinsic contractions were enhanced with neostigmine and were reduced or abolished by tetra- ethylammonium chloride and probanthine. Therefore it was concluded that these intrinsic contractions were probably myogenic in nature, because they were not dependent on any tonically active neuronal mechanism with a cholinergic synapse either at a ganglionic or at a post-ganglionic site. When the reticulo-rumen was empty or when a reticular balloon was left deflated, the resting discharges of tension receptors were either non-existent or took the form of occasional spikes sometimes aggregated into small bursts of activity. When the reticular balloon was lightly inflated the discharges increased and generally appeared as phasic bursts of activity with a few spikes in the interval between the bursts. Further inflation caused the number of spikes to increase and the interval between