The Journal of PHARMACOLOGY

And Experimental Therapeutics

A Publication of the American Society for Pharmacology and Experimental Therapeutics

March 2011 Vol. 336, No. 3 Contents

HIGHLIGHTED PAPERS 587

PERSPECTIVES IN PHARMACOLOGY

How Good Are Current Approaches to Nonclinical Evaluation of Abuse and Dependence? 588 Downloaded from Paul Moser, Toni Wolinsky, Mark Duxon, and Roger D. Porsolt

BEHAVIORAL PHARMACOLOGY In Vivo Characterization of MMP-2200, a Mixed ␦/␮ Opioid Agonist, in Mice 767

John J. Lowery, Tyler J. Raymond, Denise Giuvelis, Jean M. Bidlack, Robin Polt, and Edward J. Bilsky jpet.aspetjournals.org The Posterior Ventral Tegmental Area Mediates Alcohol-Seeking Behavior in Alcohol-Preferring Rats 857 Sheketha R. Hauser, Zheng-Ming Ding, Bruk Getachew, Jamie E. Toalston, Scott M. Oster, William J. McBride, and Zachary A. Rodd

CARDIOVASCULAR

□S Protease-Activated Receptor-1 Antagonist F 16618 Reduces Arterial Restenosis by Down-Regulation of Tumor Necrosis 643 at ASPET Journals on September 23, 2021 Factor ␣ and Matrix Metalloproteinase 7 Expression, Migration, and Proliferation of Vascular Smooth Muscle Cells Pauline Chieng-Yane, Arnaud Bocquet, Robert Le´tienne, Thierry Bourbon, Sylvie Sablayrolles, Michel Perez, Ste´phane Nicolas Hatem, Anne-Marie Lompre´, Bruno Le Grand, and Monique David-Dufilho Endothelium-Dependent Vasodilation in Human Mesenteric Artery Is Primarily Mediated by Myoendothelial Gap 701 Junctions Intermediate Conductance Calcium-Activated Kϩ Channel and Nitric Oxide Preet S. Chadha, Lu Liu, Matt Rikard-Bell, Sevvandi Senadheera, Lauren Howitt, Rebecca L. Bertrand, T. Hilton Grayson, Timothy V. Murphy, and Shaun L. Sandow In Vitro Antagonistic Properties of a New Angiotensin Type 1 Receptor Blocker, Azilsartan, in Receptor Binding 801 and Function Studies Mami Ojima, Hideki Igata, Masayuki Tanaka, Hiroki Sakamoto, Takanobu Kuroita, Yasuhisa Kohara, Keiji Kubo, Hiromitsu Fuse, Yoshimi Imura, Keiji Kusumoto, and Hideaki Nagaya Docosahexanoic Acid-Induced Coronary Arterial Dilation: Actions of 17S-Hydroxy Docosahexanoic Acid on Kϩ 891 Channel Activity Xiang Li, Song Hong, Pin-Lan Li, and Yang Zhang

□S Diosgenin Modulates Vascular Smooth Muscle Cell Function by Regulating Cell Viability, Migration, and Calcium 925 Homeostasis Mitra Esfandiarei, Julia T. N. Lam, Sahar Abdoli Yazdi, Amina Kariminia, Jorge Navarro Dorado, Boris Kuzeljevic, Harley T. Syyong, Kaiji Hu, and Cornelis van Breemen

The Journal of Pharmacology and Experimental Therapeutics (ISSN 13489 2330 RT. Indexed or abstracted by Biochemistry & Biophysics 0022-3565) is published monthly by the American Society for Pharma- Citation Index®, Biological Abstracts, BIOSIS Previews Database, Bio- cology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, Sciences Information Services, Current Awareness in Biological Sci- MD 20814-3995; email: [email protected]; Web site: aspet.org. ences, Current Contents®/Life Sciences, EMBASE/Excerpta Medica, Periodicals postage paid at Bethesda, MD, and at additional mailing Index Medicus, Medical Documentation Service®, PsycINFO, Refer- offices. POSTMASTER: Send address changes to The Journal of Phar- ence Update®, Research Alerts®, Science Citation Index®, SciSearch®, macology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, and SIIC Data Bases. Copyright © 2011 by the American Society for MD 20814-3995. Subscription rates: U.S.: $985; outside the U.S.: $1,150. Pharmacology and Experimental Therapeutics. All rights reserved. Single copy: $85. GST Tax Number for Canadian subscribers: BN: Printed in the U.S.A. CELLULAR AND MOLECULAR

□S Effect of Phospholipidosis on the Cellular Pharmacokinetics of Chloroquine 661 Nan Zheng, Xinyuan Zhang, and Gus R. Rosania Inhibition of NADPH Oxidases Prevents Chronic Ethanol-Induced Bone Loss in Female Rats 734 Jin-Ran Chen, Oxana P. Lazarenko, Kartik Shankar, Michael L. Blackburn, Charles K. Lumpkin, Thomas M. Badger, and Martin J. J. Ronis Differential Effect of Meclizine on the Activity of Human Pregnane X Receptor and Constitutive Androstane Receptor 816 Aik Jiang Lau, Guixiang Yang, Ganesh Rajaraman, Christie C. Baucom, and Thomas K. H. Chang Antitumoral Alkylphospholipids Induce Cholesterol Efflux from the Plasma Membrane in HepG2 Cells 866 Pablo Ríos-Marco, Jose´M. Jime´nez-Lo´pez, Carmen Marco, Josefa L. Segovia, and María P. Carrasco

CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

□S Role for NAD(P)H:quinone Oxidoreductase 1 and Manganese-Dependent Superoxide Dismutase in 17-(Allylamino)-17- 874 demethoxygeldanamycin-Induced Heat Shock Protein 90 Inhibition in Pancreatic Cancer Cells David Siegel, Biehuoy Shieh, Chao Yan, Jadwiga K. Kepa, and David Ross

DRUG DISCOVERY AND TRANSLATIONAL MEDICINE Downloaded from

□S A New Nonpeptidic Inhibitor of 14-3-3 Induces Apoptotic Cell Death in Chronic Myeloid Leukemia Sensitive or 596 Resistant to Imatinib Manuela Mancini, Valentina Corradi, Sara Petta, Enza Barbieri, Fabrizio Manetti, Maurizio Botta, and Maria Alessandra Santucci

Evaluation of a Stable Gonadotropin-Releasing Hormone Analog in Mice for the Treatment of Endocrine Disorders 613 jpet.aspetjournals.org and Prostate Cancer Theodora Katsila, Evangelos Balafas, George Liapakis, Patrizia Limonta, Marina Montagnani Marelli, Konstantinos Gkountelias, Theodore Tselios, Nikolaos Kostomitsopoulos, John Matsoukas, and Constantin Tamvakopoulos ELR510444, A Novel Microtubule Disruptor with Multiple Mechanisms of Action 652 A. L. Risinger, C. D. Westbrook, A. Encinas, M. Mu¨lbaier, C. M. Schultes, S. Wawro, J. D. Lewis, B. Janssen,

F. J. Giles, and S. L. Mooberry at ASPET Journals on September 23, 2021 Phenyl Ring-Substituted Lobelane Analogs: Inhibition of [3H]Dopamine Uptake at the Vesicular Monoamine Transporter-2 724 Justin R. Nickell, Guangrong Zheng, Agripina G. Deaciuc, Peter A. Crooks, and Linda P. Dwoskin The Prototypical Ranitidine Analog JWS-USC-75-IX Improves Information Processing and Cognitive Function in 751 Animal Models Alvin V. Terry, Jr., Jerry J. Buccafusco, Elizabeth J. Herman, Patrick M. Callahan, Wayne D. Beck, Samantha Warner, Leah Vandenhuerk, Kristy Bouchard, Gary M. Schwarz, Jie Gao, and James M. Chapman Acotiamide Hydrochloride (Z-338), a New Selective Acetylcholinesterase Inhibitor, Enhances Gastric Motility without 791 Prolonging QT Interval in Dogs: Comparison with Cisapride, Itopride, and Mosapride Yugo Matsunaga, Takao Tanaka, Koji Yoshinaga, Shigeru Ueki, Yuko Hori, Runa Eta, Yoshihiro Kawabata, Kazuyoshi Yoshii, Kenji Yoshida, Toshihiro Matsumura, Shigeru Furuta, Mineo Takei, Jan Tack, and Zen Itoh JTT-130, a Novel Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein, Suppresses Food Intake and Gastric 850 Emptying with the Elevation of Plasma Peptide YY and Glucagon-Like Peptide-1 in a Dietary Fat-Dependent Manner Takahiro Hata, Yasuko Mera, Yukihito Ishii, Hironobu Tadaki, Daisuke Tomimoto, Yukiharu Kuroki, Takashi Kawai, Takeshi Ohta, and Makoto Kakutani Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the 908 Hippocampus and Enhances Cognition Timothy B. Johnstone, Zhenglin Gu, Ryan F. Yoshimura, Anne-Sophie Villegier, Derk J. Hogenkamp, Edward R. Whittemore, Jin-Cheng Huang, Minhtam B. Tran, James D. Belluzzi, Jerrel L. Yakel, and Kelvin W. Gee

ENDOCRINE AND DIABETES Pharmacokinetic and Pharmacodynamic Modeling of Exendin-4 in Type 2 Diabetic Goto-Kakizaki Rats 881 Wei Gao and William J. Jusko

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells 682 and Rat Kidneys Tanecia Mitchell, Dumitru Rotaru, Hamida Saba, Robin A. J. Smith, Michael P. Murphy, and Lee Ann MacMillan-Crow Pharmacokinetic and Pharmacodynamic Characterization of an Oral Lysophosphatidic Acid Type 1 Receptor- 693 Selective Antagonist J. S. Swaney, C. Chapman, L. D. Correa, K. J. Stebbins, A. R. Broadhead, G. Bain, A. M. Santini, J. Darlington, C. D. King, C. S. Baccei, C. Lee, T. A. Parr, J. R. Roppe, T. J. Seiders, J. Ziff, P. Prasit, J. H. Hutchinson, J. F. Evans, and D. S. Lorrain

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA Silencing Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 Arrests Inflammatory Bone Loss 633 Qiyan Li, Hong Yu, Robert Zinna, Kylie Martin, Bethany Herbert, Angen Liu, Carlos Rossa, Jr., and Keith L. Kirkwood

□S A Toll-Like Receptor-4-Interacting Surfactant Protein-A-Derived Peptide Suppresses Tumor Necrosis Factor-␣ Release 672 from Mouse JAWS II Dendritic Cells Shanjana Awasthi, Kevin Brown, Catherine King, Vibhudutta Awasthi, and Rajkumar Bondugula In Vitro and In Vivo Evidence for Anti-Inflammatory Properties of 2-Methoxyestradiol 962 F. H. W. Shand, S. Y. Langenbach, C. R. Keenan, S. P. Ma, B. J. Wheaton, M. J. Schuliga, J. Ziogas, and A. G. Stewart

METABOLISM, TRANSPORT, AND PHARMACOGENOMICS How Organic Anions Accumulate in Hepatocytes Lacking Mrp2: Evidence in Rat Liver 624

Philippe Millet, Marcelle Moulin, Bruno Stieger, Youssef Daali, and Catherine M. Pastor Downloaded from Inflammatory Pain Signals an Increase in Functional Expression of Organic Anion Transporting Polypeptide 1a4 at the 827 Blood-Brain Barrier Patrick T. Ronaldson, Jessica D. Finch, Kristin M. DeMarco, Colleen E. Quigley, and Thomas P. Davis

NEUROPHARMACOLOGY jpet.aspetjournals.org Awake Rat Pharmacological Magnetic Resonance Imaging as a Translational Pharmacodynamic Biomarker: 709 Metabotropic Glutamate 2/3 Agonist Modulation of Ketamine-Induced Blood Oxygenation Level Dependence Signals Chih-Liang Chin, Jaymin Upadhyay, Gerard J. Marek, Scott J. Baker, Min Zhang, Mario Mezler, Gerard B. Fox, and Mark Day Pharmacokinetic Modeling and [123I]5-IA-85380 Single Photon Emission Computed Tomography Imaging in Baboons: 716 Optimization of Dosing Regimen for ABT-089 Chih-Liang Chin, Robert A. Carr, Daniel A. Llano, Olivier Barret, Hongyu Xu, Jeffrey Batis, Andrei O. Koren, at ASPET Journals on September 23, 2021 John P. Seibyl, Kennan C. Marsh, Gilles Tamagnan, Michael W. Decker, Mark Day, and Gerard B. Fox Amelioration of Neuropathic Pain by Novel Transient Receptor Potential Vanilloid 1 Antagonist AS1928370 in Rats 743 without Hyperthermic Effect Tomonari Watabiki, Tetsuo Kiso, Takahiro Kuramochi, Koichi Yonezawa, Noriko Tsuji, Atsuyuki Kohara, Shuichiro Kakimoto, Toshiaki Aoki, and Nobuya Matsuoka Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized 779 Studies Clifford L. Eastman, Derek R. Verley, Jason S. Fender, Tessandra H. Stewart, Eytan Nov, Giulia Curia, and Raimondo D’Ambrosio Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia 809 Paul S. Frankel, Amanda J. Hoonakker, Mario E. Alburges, Jacob W. McDougall, Lisa M. McFadden, Annette E. Fleckenstein, and Glen R. Hanson Postsynaptic and Presynaptic Group II Metabotropic Glutamate Receptor Activation Reduces Neuronal Excitability in Rat 840 Midline Paraventricular Thalamic Nucleus M. L. H. J. Hermes and L. P. Renaud Regulation of Glutamate Release by ␣7 Nicotinic Receptors: Differential Role in Methamphetamine-Induced Damage to 900 Dopaminergic and Serotonergic Terminals Nicole A. Northrop, Laura P. Smith, Bryan K. Yamamoto, and David J. Eyerman

A Substituted Anilino Enaminone Acts as a Novel Positive Allosteric Modulator of GABAA Receptors in the Mouse Brain 916 Ze-Jun Wang, Liqin Sun, Patrice L. Jackson, Kenneth R. Scott, and Thomas Heinbockel

□S meso-Transdiene Analogs Inhibit Vesicular Monoamine Transporter-2 Function and Methamphetamine-Evoked 940 Dopamine Release David B. Horton, Kiran B. Siripurapu, Seth D. Norrholm, John P. Culver, Marhaba Hojahmat, Joshua S. Beckmann, Steven B. Harrod, Agripina G. Deaciuc, Michael T. Bardo, Peter A. Crooks, and Linda P. Dwoskin The First Universal Opioid Ligand, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6- 952 methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028): Characterization of the In Vitro Profile and In Vivo Behavioral Effects in Mouse Models of Acute Pain and Cocaine-Induced Reward Taline V. Khroyan, Willma E. Polgar, Gerta Cami-Kobeci, Stephen M. Husbands, Nurulain T. Zaveri, and Lawrence Toll □S Pregabalin Modulation of Neurotransmitter Release Is Mediated by Change in Intrinsic Activation/Inactivation Properties 973

of Cav2.1 Calcium Channels Mariano N. Di Guilmi, Francisco J. Urbano, Carlota Gonzalez Inchauspe, and Osvaldo D. Uchitel

TOXICOLOGY Evidence That Botulinum Toxin Receptors on Epithelial Cells and Neuronal Cells Are Not Identical: Implications for 605 Development of a Non-Neurotropic Vaccine Md. Elias, Fetweh al-Saleem, Denise M. Ancharski, Ajay Singh, Zidoon Nasser, Rebecca M. Olson, and Lance L. Simpson Downloaded from jpet.aspetjournals.org at ASPET Journals on September 23, 2021

□S Supplemental material is available online at http://jpet.aspetjournals.org.

About the cover: Effects of ELR510444 on endothelial cell morphology. See the article by Risinger et al on page 652 of this issue.