ME T H O D S I N PH A R M A CO L O G Y A N D TOX I CO L O G Y

Series EditorY. James Kang

For further volumes:http://www.springer.com/series/7653

TRP Channels in Drug Discovery

Volume II

Edited by

Arpad Szallasi

Monmouth Medical Center, Long Branch, NJ, USA

Tamás Bíró

Medical and Health Science Center, Department of Physiology, University of Debrecen, Debrecen, Hungary

EditorsArpad SzallasiMonmouth Medical CenterLong Branch, NJ, USA

Tamás BíróMedical and Health Science Center Department of PhysiologyUniversity of DebrecenDebrecen, Hungary

ISSN 1557-2153 ISSN 1940-6053 (electronic)ISBN 978-1-62703-094-6 ISBN 978-1-62703-095-3 (eBook)DOI 10.1007/978-1-62703-095-3Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012947027

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v

Preface

With almost 600 reviews, Transient Receptor Potential (TRP) channels arguably represent today’s most extensively reviewed pharmacological targets. The literature on TRP channels is vast and still growing: It has exploded from a mere 21 papers in 1995 to over 2,000 in the past 2 years. Yet, even the most studied TRP channels like TRPV1 continue to surprise: as Bernd Nilius points it out in his Introduction, “We are still at the beginning of the beginning.”

Over the past decade, both gain- and loss-of-function mutations in TRP channels (so-called “TRP channelopathies”) have been identi fi ed in human disease states ranging from focal segmental glomerulosclerosis (TRPC6) and familial episodic pain syndrome (TRPA1) through brachyolmia and hereditary arthropathy of hand and feet (TRPV4) to mucolipido-sis type-4 (TRPML1) and amyotrophic lateralsclerosis and parkinsonism/dementia com-plex (TRPM7). These fi ndings imply a therapeutic potential for drugs targeting TRP channels in a wide variety of diseases, many with no existing satisfactory treatment options. Indeed, a number of potent, small molecule TRPV1, TRPV3, and TRPA1 antagonists have already entered clinical trials, and many more are in preclinical development.

The TRP superfamily of ion channels in humans is a diverse family of 28 cation chan-nels with varied physiological functions. Their name stems from their similarity on the sequence level to the original trp gene from Drosophila which, when mutated, resulted in a transient receptor potential in the presence of continued exposure to light. Overall, few generalizations can be made about TRP channels. Most family members share a low level of structural similarity, but some channels are very highly homologous to each other (e.g., TRPC3 and TRPC7; TRPV5 and TRPV6). Many TRP channels form functional channels as homotetramers, though heteromultimerization is not uncommon. The latter phenome-non may have important implications for drug discovery.

Consistent with their diverse structure, TRP channels also serve diverse functions including afferent sensory functions (mechanical, chemical, thermal, noxious, etc.) as well as efferent mechanisms (of growth control, cellular differentiation, vasoregulation, media-tor release, etc.). While most family members are cation channels with limited selectivity for calcium, both calcium- (TRPV5 and TRPV6) and sodium-selective (TRPM4 and TRPM5) family members exist. In addition, some TRP channels transport noncanonical cations such as iron (TRPML1), magnesium (TRPV6), or zinc (TRPA1).

Of the 28 TRP channels discovered until today, seven sense hot or warm temperatures (TRPV1 to TRPV4, TRPM2, TRPM4, and TRPM5), whereas two (TRPA1 and TRPM8) are activated by cold. Together, these channels, referred to as “thermoTRPs,” cover a wide temperature range with extremes that fall between 10 °C (TRPA1) and 53 °C (TRPV2). The temperature sensor is believed to be associated with the C terminus. In support of this model, swapping the C-terminal domain of TRPV1 with that of TRPM8 was shown to change the temperature sensitivity of TRPV1 from hot to cold.

Animal data and human genetic studies have shown that TRP channel dysfunction (“TRP channelopathy”) can cause various pathological conditions. In fact, the TRML

vi Preface

(mucolipin) and TRPP (polycystin) families were named after the human diseases they are associated with (mucolipidosis and polycystic kidney disease, respectively). The founding member of the M (melastatin) family, TRPM1, was identi fi ed via comparative analysis of genes that distinguish benign nevi and malignant melanoma. The A (ankyrin) family has only one known member (TRPA1), and its name refers to the unusually high number of ankyrin repeats at the N terminus of the channel protein. Mammalian TRP channels that are most similar to those in Drosophila are referred to as canonical (TRPC). Last, the V (vanilloid) family came into existence by expression cloning of the capsaicin receptor TRPV1.

The aim of these volumes is ambitious: They open with a series of “state-of-the-art” minireviews on the most interesting TRP channels (from TRPA1 to TRPV4), followed by a collection of cookbook-like protocol chapters describing various methodologies (ranging from capsaicin inhalation test in humans through rodent models of anxiety to stroke, can-cer, diabetes, and experimental colitis models) relevant to TRP channel research. Pain mod-els (TRPs = “Targets for Relief of Pain”) were previously detailed in our Analgesia: Methods and Protocols volume in the Methods in Molecular Biology series. Here, we focus on non-pain models in keeping with the alternative interpretation of TRPs: “Truly Remarkable Proteins.”

It is our hope that this book will be useful for graduate students in academic laborato-ries as well as for scientists developing new drugs at Pharma and clinicians interested in novel drugs in the pipeline.

Long Branch, NJ, USA Arpad SzallasiDebrecen, Hungary Tamás Biró

vii

Contents

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vContributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

PART I TRPS AND CARDIOVASCULAR DISEASE

1 TRPs to Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3José C. González-Cobos, Xuexin Zhang, Rajender K. Motiani, Kelly E. Harmon, and Mohamed Trebak

2 Anemic Zebra fi sh Models of Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . 41Xiaojing Sun and Xiaolei Xu

3 Methods to Study the Effects of TRP Channel Drugs on Vascular Endothelial Cell Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55Yan Ma, Yung-Wui Tjong, and Xiaoqiang Yao

4 Atherosclerosis Models with Cell-Mediated Calci fi cation . . . . . . . . . . . . . . . . . 75Beili Zhu

5 Models of Hypertension and Blood Pressure Recording . . . . . . . . . . . . . . . . . 91Luciana Aparecida Campos and Ovidiu Constantin Baltatu

6 Balloon Injury in Rats as a Model for Studying TRP Channel Contribution to Vascular Smooth Muscle Remodeling . . . . . . . . . . . . . . . . . . 101Wei Zhang and Mohamed Trebak

PART II TRPS AND THE BRAIN

7 TRP Channels in the Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115Antonio Reboreda

8 Investigation of the Possible Role of TRP Channels in Schizophrenia . . . . . . . 141Loris A. Chahl

9 Investigating Diseases of Dopaminergic Neurons and Melanocytes Using Zebra fi sh . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153Amanda Decker and Robert Cornell

10 A Practical Guide to Evaluating Anxiety-Related Behavior in Rodents . . . . . . . 167Caitlin J. Riebe and Carsten T. Wotjak

11 Rodent Models of Conditioned Fear: Behavioral Measures of Fear and Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187Jennifer L. McGuire, Jennifer L. Coyner, and Luke R. Johnson

12 Chick Anxiety-Depression Screening Model . . . . . . . . . . . . . . . . . . . . . . . . . . 203Stephen W. White and Kenneth J. Sufka

viii Contents

13 A Clinically Relevant Thromboembolic Stroke Model in the Aged Rat . . . . . . 211Ryan C. Turner, Alisa S. Elliott, Jason D. Huber, and Charles L. Rosen

14 Use of Cell-Stretch System to Examine the Characteristics of Mechanosensor Channels: Axonal Growth/Neuroregeneration Studies . . . . 231Koji Shibasaki

15 Methods in Neuronal Growth Cone Biology. . . . . . . . . . . . . . . . . . . . . . . . . . 239Robert J. Gasperini and Lisa Foa

PART III TRPS AND SKIN

16 Transient Receptor Potential Channels and Pruritus . . . . . . . . . . . . . . . . . . . . 255Heike Benecke, Janine Wäring, Tobias Lotts, and Sonja Ständer

17 Skin Sensitivity Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279Laurent Misery

18 Hair Follicle Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287Michael P. Philpott

PART IV TRPS AND METABOLIC DISORDERS

19 Animal Models for Type 1 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303Anish Suri and Matteo Levisetti

20 Type 2 Diabetes Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319Dorte X. Gram

21 Using Diet to Induce Metabolic Disease in Rodents . . . . . . . . . . . . . . . . . . . . 333Angela M. Gajda, Michael A. Pellizzon, and Matthew R. Ricci

22 Rodent Models to Evaluate Anti-obesity Drugs. . . . . . . . . . . . . . . . . . . . . . . . 351Sharon C. Cheetham and Helen C. Jackson

PART V TRPS: COLITIS, CANCER, THERMOSENSATION, AND MUSCULOSKELETAL DISORDERS

23 Experimental Colitis Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379Patrick A. Hughes, Stuart M. Brierley, Joel Castro, Andrea M. Harrington, and L. Ashley Blackshaw

24 Tumor Xenograft Models to Study the Role of TRP Channels in Tumorigenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 V’yacheslav Lehen’kyi, Sergii Khalimonchyk, Albin Pourtier, Maylis Raphaël, and Natalia Prevarskaya

25 Methods to Study Thermonociception in Rodents . . . . . . . . . . . . . . . . . . . . . 401Kata Bölcskei

26 Methods for the Assessment of Heat Perception in Humans . . . . . . . . . . . . . . 419Michael F. Crutchlow and Joel D. Greenspan

ix Contents

27 Collagen Antibody-Induced Arthritis: A Disease-Relevant Model for Studies of Persistent Joint Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437Katalin Sandor, Kutty Selva Nandakumar, Rikard Holmdahl, and Camilla I. Svensson

28 Animal Models of Muscular Dystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457Yuko Iwata and Shigeo Wakabayashi

Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481

xi

Contributors

OVIDIU CONSTANTIN BALTATU • Universidade Camilo Castelo Branco , São José dos Campos São Paulo , Brazil

HEIKE BENECKE • Department of Cell Physiology , Ruhr-University Bochum , Bochum , Germany

L. ASHLEY BLACKSHAW • Nerve-Gut Research Laboratory, Department of Medicine, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia; Department of Gastroenterology & Hepatology , Hanson Institute, Royal Adelaide Hospital , Adelaide , SA , Australia; Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia

KATA BÖLCSKEI • Analgesic Research Laboratory , University of Pécs , Pécs , Hungary; Laboratory of Neuropharmacology, Pharmacological and Drug Safety Research , Gedeon Richter Plc. , Budapest , Hungary

STUART M. BRIERLEY • Nerve-Gut Research Laboratory, Department of Medicine, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia; Department of Gastroenterology & Hepatology , Hanson Institute, Royal Adelaide Hospital , Adelaide , SA , Australia; Department of Physiology, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia

LUCIANA APARECIDA CAMPOS • Universidade Camilo Castelo Branco , São José dos Campos São Paulo , Brazil

JOEL CASTRO • Nerve-Gut Research Laboratory, Department of Medicine, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia; Department of Gastroenterology & Hepatology , Hanson Institute, Royal Adelaide Hospital , Adelaide , SA , Australia

LORIS A. CHAHL • School of Biomedical Sciences and Pharmacy, University of Newcastle , Newcastle , NSW , Australia; Schizophrenia Research Institute , Sydney , NSW , Australia

SHARON C. CHEETHAM • RenaSci Limited , BioCity Nottingham , UK ROBERT CORNELL • Department of Anatomy and Cell Biology ,

Carver College of Medicine, University of Iowa , Iowa City , IA , USA JENNIFER L. COYNER • Psychiatry and Neuroscience, School of Medicine, Uniformed Services

University (USU) , Bethesda , MD , USA; Center for Neuroscience and Regenerative Medicine (CNRM) , Bethesda , MD , USA

MICHAEL F. CRUTCHLOW • Merck Sharp & Dohme Corp. , Whitehouse Station , NJ , USA AMANDA DECKER • Department of Anatomy and Cell Biology , Carver College of Medicine,

University of Iowa , Iowa City , IA , USA ALISA S. ELLIOTT • Department of Neurosurgery and The Center for Neuroscience ,

West Virginia University, School of Medicine , Morgantown , WV , USA LISA FOA • School of Medicine, University of Tasmania , Tasmania , Australia ANGELA M. GAJDA • Research Diets, Inc. , New Brunswick , NJ , USA

xii Contributors

ROBERT J. GASPERINI • Menzies Research Institute Tasmania, University of Tasmania , Tasmania , Australia

JOSÉ C. GONZÁLEZ-COBOS • The Center for Cardiovascular Sciences , Albany Medical College , Albany , NY , USA

DORTE X. GRAM • XENIA PHARMA , Copenhagen , Denmark; Department of Science, System, and Models , Roskilde University , Roskilde , Denmark

JOEL D. GREENSPAN • Department of Neural and Pain Sciences and Brotman Facial Pain Center , University of Maryland Dental School , Baltimore , MD , USA

KELLY E. HARMON • The Center for Cardiovascular Sciences , Albany Medical College , Albany , NY , USA

ANDREA M. HARRINGTON • Nerve-Gut Research Laboratory, Department of Medicine, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia; Department of Gastroenterology & Hepatology , Hanson Institute, Royal Adelaide Hospital , Adelaide , SA , Australia

RIKARD HOLMDAHL • Medical In fl ammation Research, Department of Medical Biochemistry and Biophysics , Karolinska Institute , Stockholm , Sweden

JASON D. HUBER • The Center for Neuroscience and Department of Basic Pharmaceutical Sciences , West Virginia University, School of Medicine , Morgantown , WV , USA

PATRICK A. HUGHES • Nerve-Gut Research Laboratory, Department of Medicine, Faculty of Health Sciences , The University of Adelaide , Adelaide , SA , Australia; Department of Gastroenterology & Hepatology , Hanson Institute, Royal Adelaide Hospital , Adelaide , SA , Australia; Leukocyte Biology Laboratory , Women’s and Children’s Health Research Institute , North Adelaide , SA , Australia

YUKO IWATA • Department of Molecular Physiology , National Cerebral and Cardiovascular Center Research Institute , Osaka , Japan

HELEN C. JACKSON • RenaSci Limited , BioCity, Nottingham , UK LUKE R. JOHNSON • Psychiatry and Neuroscience, School of Medicine, Uniformed Services

University (USU) , Bethesda , MD , USA; Center for the Study of Traumatic Stress (CSTS) , Bethesda , MD , USA; Center for Neuroscience and Regenerative Medicine (CNRM) , Bethesda , MD , USA

SERGII KHALIMONCHYK • INSERM U-1003, Equipe labellisée par la Ligue Nationale contre le cancer , Villeneuve d’Ascq , France S. Khalimonchyk Université des Sciences et Technologies de Lille (USTL) , Villeneuve d’Ascq , France

V’YACHESLAV LEHEN’KYI • INSERM U-1003, Equipe labellisée par la Ligue Nationale contre le cancer , Villeneuve d’Ascq , France; Université des Sciences et Technologies de Lille (USTL) , Villeneuve d’Ascq , France

MATTEO LEVISETTI • Global Clinical Development , P fi zer , La Jolla , CA , USA TOBIAS LOTTS • Department of Dermatology, Clinical Neurodermatology ,

University of Münster , Münster , Germany YAN MA • Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences,

Chinese University of Hong Kong , Hong Kong , China JENNIFER L. MCGUIRE • Psychiatry and Neuroscience , School of Medicine,

Uniformed Services University (USU) , Bethesda , MD , USA LAURENT MISERY • Department of Dermatology , University Hospital of Brest

and Laboratory of Neurosciences of Brest, University of Western Brittany , Brest , France

xiii Contributors

RAJENDER K. MOTIANI • The Center for Cardiovascular Sciences , Albany Medical College , Albany , NY , USA

KUTTY SELVA NANDAKUMAR • Medical In fl ammation Research, Department of Medical Biochemistry and Biophysics , Karolinska Institute , Stockholm , Sweden

MICHAEL A. PELLIZZON • Research Diets, Inc. , New Brunswick , NJ , USA MICHAEL P. PHILPOTT • Centre for Cutaneous Research , Blizard Institute, Barts

and The London School of Medicine and Dentistry, Queen Mary College University of London , London , UK

ALBIN POURTIER • Institut de Biologie, UMR-8161, CNRS/Universités de Lille1 et Lille2/Institut Pasteur de Lille , Lille , France

NATALIA PREVARSKAYA • INSERM U-1003, Equipe labellisée par la Ligue Nationale contre le cancer , Villeneuve d’Ascq , France; Université des Sciences et Technologies de Lille (USTL) , Villeneuve d’Ascq , France

MAYLIS RAPHAËL • INSERM U-1003, Equipe labellisée par la Ligue Nationale contre le cancer , Villeneuve d’Ascq , France; Université des Sciences et Technologies de Lille (USTL) , Villeneuve d’Ascq , France

ANTONIO REBOREDA • Section of Physiology, Department of Functional Biology and Health Sciences , School of Biology, University of Vigo , Vigo, Pontevedra , Spain

MATTHEW R. RICCI • Research Diets, Inc. , New Brunswick , NJ , USA CAITLIN J. RIEBE • Max Planck Institute of Psychiatry , Munich , Germany CHARLES L. ROSEN • Department of Neurosurgery and The Center for Neuroscience ,

West Virginia University, School of Medicine , Morgantown , WV , USA KATALIN SANDOR • Department of Physiology and Pharmacology , Karolinska Institute ,

Stockholm , Sweden KOJI SHIBASAKI • Department of Molecular and Cellular Neurobiology , Gunma University

Graduate School of Medicine , Maebashi , Japan SONJA STÄNDER • Department of Dermatology, Clinical Neurodermatology , University of

Münster , Münster , Germany KENNETH J. SUFKA • Department of Psychology, Department of Pharmacology , Research

Institute of Pharmaceutical Sciences, University of Mississippi , Oxford , MI , USA XIAOJING SUN • Department of Biochemistry and Molecular Biology , Mayo Clinic , Rochester ,

MN , USA; Division of Cardiovascular Diseases, Department of Medicine , Mayo Clinic , Rochester , MN , USA

ANISH SURI • Discovery Immunology , Bristol Myers Squibb , Princeton , NJ , USA CAMILLA I. SVENSSON • Department of Physiology and Pharmacology , Karolinska Institute ,

Stockholm , Sweden YUNG-WUI TJONG • Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences,

Chinese University of Hong Kong , Hong Kong , China MOHAMED TREBAK • The Center for Cardiovascular Sciences , Albany Medical College ,

Albany , NY , USA RYAN C. TURNER • Department of Neurosurgery and The Center for Neuroscience ,

West Virginia University, School of Medicine , Morgantown , WV , USA SHIGEO WAKABAYASHI • Department of Molecular Physiology , National Cerebral

and Cardiovascular Center Research Institute , Osaka , Japan JANINE WÄRING • Department of Cell Physiology , Ruhr-University Bochum , Bochum , Germany

xiv Contributors

STEPHEN W. WHITE • Department of Psychology , University of Mississippi , Oxford , MI , USA CARSTEN T. WOTJAK • Max Planck Institute of Psychiatry , Munich , Germany XIAOLEI XU • Department of Biochemistry and Molecular Biology , Mayo Clinic , Rochester ,

MN , USA; Division of Cardiovascular Diseases, Department of Medicine , Mayo Clinic , Rochester , MN , USA

XIAOQIANG YAO • Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, Chinese University of Hong Kong , Hong Kong , China

WEI ZHANG • The Center for Cardiovascular Sciences , Albany Medical College , Albany , NY , USA

XUEXIN ZHANG • The Center for Cardiovascular Sciences , Albany Medical College , Albany , NY , USA

BEILI ZHU • Janey and Dolph Briscoe Division of Cardiology, Department of Medicine , The University of Texas Health Science Center at San Antonio , San Antonio , TX , USA