Gastrointestinal Pharmacology PDF
Preview Gastrointestinal Pharmacology
Handbook of Experimental Pharmacology 239 Beverley Greenwood-Van Meerveld Editor Gastrointestinal Pharmacology Handbook of Experimental Pharmacology Volume 239 Editor-in-Chief J.E.Barrett,Philadelphia EditorialBoard V.Flockerzi,Homburg M.A.Frohman,StonyBrook,NY P.Geppetti,Florence F.B.Hofmann,Mu¨nchen M.C.Michel,Mainz C.P.Page,London W.Rosenthal,Berlin K.Wang,Beijing More information about this series at http://www.springer.com/series/164 Beverley Greenwood-Van Meerveld Editor Gastrointestinal Pharmacology Editor BeverleyGreenwood-VanMeerveld Neuroscience/Physiology TheUniversityofOklahomaHealthSciencesCenter OklahomaCity,Oklahoma USA ISSN0171-2004 ISSN1865-0325 (electronic) HandbookofExperimentalPharmacology ISBN978-3-319-56359-6 ISBN978-3-319-56360-2 (eBook) DOI10.1007/978-3-319-56360-2 LibraryofCongressControlNumber:2017937312 #SpringerInternationalPublishingAG2017 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthis book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained hereinor for anyerrors oromissionsthat may havebeenmade. Thepublisher remainsneutralwith regardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations. Printedonacid-freepaper ThisSpringerimprintispublishedbySpringerNature TheregisteredcompanyisSpringerInternationalPublishingAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface In 1982, two volumes of the Handbook of Experimental Pharmacology edited by ProfessorGiulioBertaccini,M.D.,addressingMediatorsandDrugsinGastrointes- tinal Motility I and II were published. In 1993, David R. Brown, Ph.D., edited a volumeintheHandbookofExperimentalPharmacologyonGastrointestinalRegu- latoryPeptides.Over20yearslaterthislatestvolumeoftheHandbookofExperi- mental Pharmacology aims to connect current ideas and concepts about gastrointestinal (GI) disorders with the search for novel therapeutics. Towards thisgoal,thefollowingchapterswillprovideatimelystate-of-the-artoverviewof the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.GI disordersrank among the mostprevalentdisorders, withthemostcommonincludingesophagealandswallowingdisorders,gastricand peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Some of these disorders areorganicinvolvingpathologicaldamagetotheGItractasseeninIBDwhenthe bowel becomes inflamed and damaged, leading to abdominal pain, diarrhea, and rectal bleeding. Other GI disorders such as IBS are termed “functional” disorders because they lack a structural or biochemically defined cause. Recent estimates suggest that one in four people suffer from a functional bowel disorder and they represent40%ofGIproblemsseenbyphysicians.Themajorsymptomsofcommon GIdisordersincluderecurrentabdominalpainandbloating,heartburn,indigestion/ dyspepsia, nausea and vomiting, diarrhea, and constipation. Despite GI disorders placing a growing burden on today’s healthcare system, many GI disorders are difficult to diagnose and the symptoms are not effectively managed. In addition, many patients with GI disorders donotbenefit fromthe currentlyavailable thera- peutics.Noveleffectivetherapeuticsarethusurgentlyneeded.Currently,thereare alimitednumberofmedicationsavailableorapprovedtotreatGIdisordersdue,in part, to a lack of knowledge of the exact mechanisms underlying GI motility, absorption, secretion, inflammation, and sensation. Although significant gaps in theunderstandingofGIdisordersstillexist,newtherapiesarelikelytoemergefrom current research and development. The immune system in the gut is currently offering a wide variety of therapeutic targets to treat IBD, whereas concepts that have emerged to treat GI dysmotility, abdominal pain and IBS, include the v vi Preface brain-gut axis linking the nervous system in the GI tract to the CNS. The gut microbiome is currently an area of active research. Moreover, our understanding of the gut microbiota remains in its infancy; however major advances linking the intestinalmicrobiometothebrain-gutaxisarelikelyovertheupcomingyearsand will offer new therapeutic targets for the development of novel drugs to treat GI disorders. IamimmenselygratefultoJamesBarrettforinvitingmetoserveastheEditorof this volume on Gastrointestinal Pharmacology in the Handbook of Experimental Pharmacology book series. I would like to thank the editorial staff from Springer foralltheirsupport.Mostimportantly,thesuccessofthisvolumeonGastrointesti- nalPharmacologyisduetoeachofmycolleagueswhogenerouslycontributedtheir expertise and time to preparing such outstanding chapters for this volume of the Handbook of Experimental Pharmacology. I am indebted to this team of highly distinguishedleadersintheGIfield.Wehopethatthisvolumeofthehandbookwill serve as an essential reference to investigators and scholars involved in basic and clinicalGIresearchaswellasindividualstreatingpatientswithGIdisorders. OklahomaCity,Oklahoma,USA BeverleyGreenwood-VanMeerveld Contents GastrointestinalPhysiologyandFunction. . . . . . . . . . . . . . . . . . . . . . . 1 BeverleyGreenwood-VanMeerveld,AnthonyC.Johnson, andDavidGrundy UpperGIDisorders:PathophysiologyandCurrentTherapeutic Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 HenryP.Parkman PostoperativeIleus:Pathophysiology,CurrentTherapeutic Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 N.Stakenborg,P.J.Gomez-Pinilla,andG.E.Boeckxstaens Constipation:PathophysiologyandCurrentTherapeutic Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 AmolSharmaandSatishRao IrritableBowelSyndrome:PathophysiologyandCurrent TherapeuticApproaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 MichaelCamilleriandAlexanderC.Ford InflammatoryBowelDisease:PathophysiologyandCurrent TherapeuticApproaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 BincyP.Abraham,TasneemAhmed,andTauseefAli GastrointestinalPharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 MiguelSapsandAdrianMiranda Sex-RelatedDifferencesinGIDisorders. . . . . . . . . . . . . . . . . . . . . . . . 177 DawnK.PrusatorandLinChang AbnormalBarrierFunctioninGastrointestinalDisorders. . . . . . . . . . 193 RicardFarre´ andMar´ıaVicario IrritableBowelSyndromeandStress-RelatedPsychiatric Co-morbidities:FocusonEarlyLifeStress. . . . . . . . . . . . . . . . . . . . . 219 SiobhainM.O’Mahony,GerardClarke,TimothyG.Dinan, andJohnF.Cryan vii viii Contents NeuroimmuneModulationofGutFunction. . . . . . . . . . . . . . . . . . . . . 247 TerezShea-DonohueandJosephF.Urban,Jr. TheRoleoftheGastrointestinalMicrobiotainVisceralPain. . . . . . . . 269 KieranRea,SiobhainM.O’Mahony,TimothyG.Dinan, andJohnF.Cryan CriticalEvaluationofAnimalModelsofGastrointestinalDisorders. . . 289 AnthonyC.JohnsonandBeverleyGreenwood-VanMeerveld SerotonergicMechanismsRegulatingtheGITract:Experimental EvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . . . . . . . . . . . . 319 NatalieTerryandKaraGrossMargolis CannabinoidReceptorsinRegulatingtheGITract:Experimental EvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . . . . . . . . . . . . 343 UlrikeTaschler,CarinaHasenoehrl,MartinStorr,andRudolfSchicho InsightsintotheRoleofOpioidReceptorsintheGITract: ExperimentalEvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . 363 JamesJ.GalliganandCatiaSternini GhrelinandMotilinControlSystemsinGIPhysiologyand Therapeutics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 GarethJ.Sanger,JohnBroad,BridCallaghan,andJohnB.Furness CentrallyTargetedPharmacotherapyforChronicAbdominalPain: UnderstandingandManagement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417 HansT€ornblomandDouglasA.Drossman Index. . . . .. . . . .. . . . . .. . . . .. . . . . .. . . . .. . . . .. . . . . .. . . . .. . . 441 Gastrointestinal Physiology and Function Beverley Greenwood-Van Meerveld, Anthony C. Johnson, and David Grundy Contents 1 Introduction................................................................................... 2 2 BasicAnatomyoftheGITract.............................................................. 3 2.1 BasicFunctionsoftheGITract:GIMotility.......................................... 4 2.2 BasicFunctionsoftheGITract:GISecretionandAbsorption...................... 5 2.3 BasicFunctionsoftheGITract:GIBarrierFunction................................ 5 3 NeuralControloftheGITract............................................................... 6 3.1 EntericNervousSystem................................................................ 6 3.2 ExtrinsicInnervationoftheGITract.................................................. 7 3.3 VisceralAfferentSensitization......................................................... 7 3.4 CentralSensitization.................................................................... 8 4 GIPathophysiology........................................................................... 9 4.1 StressandtheGITract................................................................. 10 4.2 GutImmuneSystem.................................................................... 11 4.3 EffectofAgingontheGITract....................................................... 12 5 SummaryandConclusion.................................................................... 13 References........................................................................................ 13 Abstract Thegastrointestinal(GI)systemisresponsibleforthedigestionand absorp- tionofingestedfoodandliquids.DuetothecomplexityoftheGItractandthe B.Greenwood-VanMeerveld(*) UniversityofOklahomaandVAMedicalCenter,OklahomaCity,OK,USA e-mail:[email protected] A.C.Johnson UniversityofOklahoma,OklahomaCity,OK,USA e-mail:[email protected] D.Grundy UniversityofSheffield,Sheffield,UK e-mail:D.Grundy@sheffield.ac.uk #SpringerInternationalPublishingAG2017 1 B.Greenwood-VanMeerveld(ed.),GastrointestinalPharmacology, HandbookofExperimentalPharmacology239,DOI10.1007/164_2016_118
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