The Journal of PHARMACOLOGY

And Experimental Therapeutics

A Publication of the American Society for Pharmacology and Experimental Therapeutics

July 2007 Vol. 322, No. 1 Contents

BEHAVIORAL PHARMACOLOGY Decrease in N-Methyl-D-aspartic Acid Receptor-NR2B Subunit Bichoy H. Gabra, Fay K. Kessler, 186 Levels by Intrathecal Short-Hairpin RNA Blocks Group I Joseph K. Ritter, William L. Dewey, and Metabotropic Glutamate Receptor-Mediated Hyperalgesia Forrest L. Smith Downloaded from Antibodies to Nerve Growth Factor Reverse Established Kenneth D. Wild, Di Bian, Dawn Zhu, 282 Tactile Allodynia in Rodent Models of Neuropathic Pain James Davis, Anthony W. Bannon, without Tolerance Tie J. Zhang, and Jean-Claude Louis Induction by Antipsychotics of “Win-Shift” in the Drug Francis Colpaert, Wouter Koek, 288 Discrimination Paradigm Mark Kleven, and Joel Besnard

CARDIOVASCULAR jpet.aspetjournals.org Direct Effects of Nicotine on Contractility of the Uterine DaLiao Xiao, Xiaohui Huang, Shumei Yang, 180 Artery in Pregnancy and Lubo Zhang Chronic Treatment with Carvedilol Improves Ca2؉- K. Brixius, R. Lu, B. Boelck, S. Grafweg, 222 Dependent ATP Consumption in Triton X-Skinned Fiber F. Hoyer, C. Pott, U. Mehlhorn, W. Bloch, Preparations of Human Myocardium and R. H. G. Schwinger Modulation of Sympathetic Activity by Tissue Plasminogen Ulrich Schaefer, Sandra Vorlova, 265 at ASPET Journals on September 23, 2021 Activator Is Independent of Plasminogen and Urokinase Takuji Machida, Jerry P. Melchor, Sidney Strickland, and Roberto Levi An in Vitro Study with an Ussing Chamber Showing That Bita Moazed and Linda M. Hiebert 299 Unfractionated Heparin Crosses Rat Gastric Mucosa ␴ 2-Receptor Ligand-Mediated Inhibition of Inwardly Laurent Monassier, Boris Manoury, 341 ,Rectifying K؉ Channels in the Heart Chloe´Bellocq, Jacques Weissenburger Hugues Greney, Diane Zimmermann, Jean-Daniel Ehrhardt, Patrice Jaillon, Isabelle Baro´, and Pascal Bousquet Biomarker Optimization to Track the Antithrombotic and William A. Schumacher, 369 Hemostatic Effects of Clopidogrel in Rats Jeffrey S. Bostwick, Martin L. Ogletree, Anne B. Stewart, Thomas E. Steinbacher, Ji Hua, Laura A. Price, Pancras C. Wong, and Robert P. Rehfuss

CELLULAR AND MOLECULAR Nicotine and Ethanol Activate Protein Kinase A Yuichiro Inoue, Lina Yao, 23 ␤␥ Synergistically via Gi Subunits in Nucleus F. Woodward Hopf, Peidong Fan, Accumbens/Ventral Tegmental Cocultures: The Role of Zhan Jiang, Antonello Bonci, and

Dopamine D1/D2 and Adenosine A2A Receptors Ivan Diamond

□S Neuroprotection by Small Molecule Activators of the Nerve Bo Lin, Michael C. Pirrung, Liu Deng, 59 Growth Factor Receptor Zhitao Li, Yufa Liu, and Nicholas J. G. Webster

The Journal of Pharmacology and Experimental Therapeutics (ISSN Single copy: $85.00. GST Tax Number for Canadian subscribers: 0022-3565) is published monthly by the American Society for Phar- BN:13489 2330 RT. Indexed or abstracted by Biochemistry & Bio- macology and Experimental Therapeutics, 9650 Rockville Pike, physics Citation Index®, Biological Abstracts, BIOSIS Previews Data- Bethesda, MD 20814-3995; email: [email protected]; web site: base, BioSciences Information Services, Current Awareness in Bio- www.aspet.org. Periodicals postage paid at Bethesda, MD, and at ad- logical Sciences, Current Contents®/Life Sciences, EMBASE/ ditional mailing offices. POSTMASTER: Send address changes to The Excerpta Medica, Index Medicus, Medical Documentation Service®, Journal of Pharmacology and Experimental Therapeutics, 9650 Rock- PsycINFO, Reference Update®, Research Alert®, Science Citation ville Pike, Bethesda, MD 20814-3995. Subscription rates: U.S.: $850.00 Index®, SciSearch®, and SIIC Data Bases. Copyright © 2007 by the for institutions and $370.00 for non-ASPET members. Outside the American Society for Pharmacology and Experimental Therapeutics. U.S.: $999.00 for institutions and $519.00 for non-ASPET members. All rights reserved. Printed in the U.S.A. Beryllium Induces Premature Senescence in Human Shannon S. A. Coates, Bruce E. Lehnert, 70 Fibroblasts Sunil Sharma, Susan M. Kindell, and Ronald K. Gary

□S Oxyntomodulin Differentially Affects Glucagon-Like Peptide-1 Rasmus Jorgensen, Valentina Kubale, 148 ␤ ␣ Receptor -Arrestin Recruitment and Signaling through G s Milka Vrecl, Thue W. Schwartz, and Christian E. Elling In Vitro Pharmacology of Clinically Used Central Nervous R. A. Bakker, M. W. Nicholas, T. T. Smith, 172

System-Active Drugs as Inverse H1 Receptor Agonists E. S. Burstein, U. Hacksell, H. Timmerman, R. Leurs, M. R. Brann, and D. M. Weiner Apomine Enhances the Antitumor Effects of Lovastatin on Anke J. Roelofs, Claire M. Edwards, 228 Myeloma Cells by Down-Regulating 3-Hydroxy-3- R. Graham G. Russell, F. Hal Ebetino, methylglutaryl-Coenzyme A Reductase Michael J. Rogers, and Philippa A. Hulley

CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY Tumor Priming Enhances Delivery and Efficacy of Dan Lu, M. Guillaume Wientjes, Ze Lu, and 80 Nanomedicines Jessie L.-S. Au Combination Silencer RNA (siRNA) Targeting Bcl-2 Aleksandra A. Pandyra, Randal Berg, 123 Antagonizes siRNA against Thymidylate Synthase in Human Mark Vincent, and James Koropatnick Tumor Cell Lines

ENDOCRINE AND DIABETES Downloaded from Nateglinide and Mitiglinide, but Not Sulfonylureas, Induce Makoto Shigeto, Masashi Katsura, 1 Insulin Secretion through a Mechanism Mediated by Calcium Masafumi Matsuda, Seitaro Ohkuma, and Release from Endoplasmic Reticulum Kohei Kaku Pharmacological Profile of the Thyroid Hormone Receptor Gary J. Grover, Celeste Dunn, 385 Antagonist NH3 in Rats Ngoc-Ha Nguyen, Jamie Boulet, Gao Dong, Jason Domogauer, Peter Barbounis, and jpet.aspetjournals.org Thomas S. Scanlan

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL Cisplatin-Induced Acute Renal Failure Is Associated with an Sarah Faubel, Eli C. Lewis, 8 Increase in the Cytokines Interleukin (IL)-1␤, IL-18, IL-6, Leonid Reznikov, Danica Ljubanovic, and Neutrophil Infiltration in the Kidney Thomas S. Hoke, Hilary Somerset,

Dong-Jin Oh, Lawrence Lu, at ASPET Journals on September 23, 2021 Christina L. Klein, Charles A. Dinarello, and Charles L. Edelstein Conditional Deletion of Cytochrome P450 Oxidoreductase in Robert D. Finn, Aileen W. McLaren, 40 the Liver and Gastrointestinal Tract: A New Model for Dianne Carrie, Colin J. Henderson, and Studying the Functions of the P450 System C. Roland Wolf Role of Transforming Growth Factor ␤ in Rat Bladder Maurits M. Barendrecht, 117 Smooth Muscle Cell Proliferation Arthur C. M. Mulders, Henk van der Poel, Maurice J. B. van den Hoff, Martina Schmidt, and Martin C. Michel Centrally Administered Nociceptin/Orphanin FQ (N/OFQ) Melissa A. Burmeister and 324 Evokes Bradycardia, Hypotension, and Diuresis in Mice via Daniel R. Kapusta Activation of Central N/OFQ Peptide Receptors

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA Neuroinflammation and Behavioral Abnormalities after M. C. Zerrate, M. Pletnikov, S. L. Connors, 16 Neonatal Terbutaline Treatment in Rats: Implications for D. L. Vargas, F. J. Seidler, Autism A. W. Zimmerman, T. A. Slotkin, and C. A. Pardo Attenuation of Ozone-Induced Airway Inflammation and Alison S. Williams, Razao Issa, 351

Hyper-Responsiveness by c-Jun NH2 Terminal Kinase Sum Yee Leung, Puneeta Nath, Inhibitor SP600125 Gregory D. Ferguson, Brydon L. Bennett, Ian M. Adcock, and Kian Fan Chung

METABOLISM, TRANSPORT, AND PHARMACOGENOMICS

□S Central Nervous System Drug Disposition: The Relationship Scott G. Summerfield, Kevin Read, 205 between in Situ Brain Permeability and Brain Free Fraction David J. Begley, Tanja Obradovic, Ismael J. Hidalgo, Sara Coggon, Ann V. Lewis, Rod A. Porter, and Phil Jeffrey Accelerated Urinary Excretion of Methylmercury following Michael S. Madejczyk, David A. Aremu, 378 Administration of Its Antidote N-Acetylcysteine Requires Tracey A. Simmons-Willis, Mrp2/Abcc2, the Apical Multidrug Resistance-Associated Thomas W. Clarkson, and Protein Nazzareno Ballatori Rifaximin Is a Gut-Specific Human Pregnane X Receptor Xiaochao Ma, Yatrik M. Shah, 391 Activator Grace L. Guo, Ting Wang, Kristopher W. Krausz, Jeffrey R. Idle, and Frank J. Gonzalez Doxorubicin Degradation in Cardiomyocytes Pierantonio Menna, Emanuela Salvatorelli, 408 and Giorgio Minotti

NEUROPHARMACOLOGY Using Hapten Design to Discover Therapeutic Monoclonal Eric C. Peterson, Melinda Gunnell, 30 Antibodies for Treating Methamphetamine Abuse Yingni Che, Robyn L. Goforth, F. Ivy Carroll, Ralph Henry, Huimin Liu, and S. Michael Owens Competitive Antagonism between the Nicotinic Allosteric Cristiane Lopes, Edna F. R. Pereira, 48 Potentiating Ligand Galantamine and Kynurenic Acid at ␣7* Hui-Qiu Wu, Puranik Purushottamachar, Nicotinic Receptors Vincent Njar, Robert Schwarcz, and Edson X. Albuquerque In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Esther Berrocoso and Juan Antonio Mico 101 ␣ Role of Opioid, 2-Adrenergic, and 5-Hydroxytryptamine1A Receptors Olanzapine Increases RGS7 Protein Expression via Rakesh K. Singh, Ju Shi, 133 Stimulation of the Janus Tyrosine Kinase-Signal Transducer Bozena W. Zemaitaitis, and Nancy A. Muma Downloaded from and Activator of Transcription Signaling Cascade Region-Specific Overexpression of P-glycoprotein at the E. A. van Vliet, R. van Schaik, 141 Blood-Brain Barrier Affects Brain Uptake of Phenytoin in P. M. Edelbroek, R. A. Voskuyl, S. Redeker, Epileptic Rats E. Aronica, W. J. Wadman, and J. A. Gorter Selectivity of ␦- and ␬-Opioid Ligands Depends on the Route Mary M. Lunzer and Philip S. Portoghese 166 of Central Administration in Mice jpet.aspetjournals.org Flufenamic Acid Bi-Directionally Modulates the Transient Zheng-Ge Zhao, Man Zhang, Xi-Min Zeng, 195 ,Outward K؉ Current in Rat Cerebellar Granule Cells Xiao-Wei Fei, Lin-Yun Liu Zhi-Hong Zhang, Yan-Ai Mei Pharmacological Effects of Ephedrine Alkaloids on Human Guoyi Ma, Supriya A. Bavadekar, 214 ␣ ␣ 1- and 2-Adrenergic Receptor Subtypes Yolande M. Davis, Shilpa G. Lalchandani, Rangaswamy Nagmani, Brian T. Schaneberg, Ikhlas A. Khan, and Dennis R. Feller at ASPET Journals on September 23, 2021 The Fatty Acid Amide Hydrolase Inhibitor URB597 Roberto Russo, Jesse LoVerme, 236 (Cyclohexylcarbamic Acid 3-Carbamoylbiphenyl-3-yl Ester) Giovanna La Rana, Timothy R. Compton, Reduces Neuropathic Pain after Oral Administration in Mice Jeff Parrott, Andrea Duranti, Andrea Tontini, Marco Mor, Giorgio Tarzia, Antonio Calignano, and Daniele Piomelli Behavioral Cross-Tolerance between Repeated Intracerebellar Aaron D. Smith and M. Saeed Dar 243 Nicotine and Acute ⌬9-Tetrahydrocannabinol-Induced Cerebellar Ataxia: Role of Cerebellar Nitric Oxide A Novel Family of Potent Negative Allosteric Modulators of Kamondanai Hemstapat, Herve Da Costa, 254 Group II Metabotropic Glutamate Receptors Yi Nong, Ashley E. Brady, Qingwei Luo, Colleen M. Niswender, Gilles D. Tamagnan, and P. Jeffrey Conn Edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one), a Radical Toshiyuki Kawasaki, Kotaro Ishihara, 274 Scavenger, Prevents 1-Methyl-4-phenyl-1,2,3,6- Yukio Ago, Akemichi Baba, and tetrahydropyridine-Induced Neurotoxicity in the Substantia Toshio Matsuda Nigra but Not the Striatum Chronic Nicotine Differentially Regulates ␣6- and ␤3- David C. Perry, Danyan Mao, 306 Containing Nicotinic Cholinergic Receptors in Rat Brain Allison B. Gold, J. Michael McIntosh, John C. Pezzullo, and Kenneth J. Kellar Wash-Resistantly Bound Xanomeline Inhibits Acetylcholine E. Machova´, J. Jakubı´k, E. E. El-Fakahany, 316

Release by Persistent Activation of Presynaptic M2 and M4 and V. Dolezal Muscarinic Receptors in Rat Brain

Rapid Stimulation of Presynaptic Serotonin Transport by A3 Chong-Bin Zhu, Jennifer A. Steiner, 332 Adenosine Receptors Jaclyn L. Munn, Lynette C. Daws, William A. Hewlett, and Randy D. Blakely Tolerance to the Antinociceptive and Antiexudative Effects of Vı´ctor Ferna´ndez-Duen˜as, Olga Pol, 360 Morphine in a Murine Model of Peripheral Inflammation Paula Garcı´a-Nogales, Laura Herna´ndez, Eula`lia Planas, and Margarita M. Puig Nicotine Dependence and Reward Differ between Adolescent D. Kota, B. R. Martin, S. E. Robinson, and 399 and Adult Male Mice M. I. Damaj TOXICOLOGY

□S Proteomic Analysis of Alternative Protein Tyrosine Marjo de Graauw, Sylvia Le De´ve´dec, 89 Phosphorylation in 1,2-Dichlorovinyl-Cysteine-Induced Ine Tijdens, Mirjam B. Smeets, Cytotoxicity in Primary Cultured Rat Renal Proximal Andre´M. Deelder, and Bob van de Water Tubular Cells Reversal of Lead-Induced Neuronal Apoptosis by Chelation Swaran J. S. Flora, Geetu Saxena, and 108 Treatment in Rats: Role of Reactive Oxygen Species and Ashish Mehta Intracellular Ca2؉ Apoptosis in Microencapsulated Juvenile Rabbit Chondrocytes Zhi-guo Sheng, Shuangqing Peng, 155 ␤ Induced by Ofloxacin: Role Played by 1-Integrin Receptor Chang-yong Wang, Hong-bo Li, Ravindra K. Hajela, Yim-ei Wang, Qian-qian Li, Mi-feng Liu, Yan-sheng Dong, and Gang Han

LETTERS TO THE EDITOR Comments on “Cannabimimetic Properties of Ajulemic Acid” Matthias Karst 420 Comments on “Anti-Influenza Prodrug Oseltamivir Is Stephen Fowler, Siaˆn M. Lennon, 422 Activated by Carboxylesterase Human Carboxylesterase 1, Gerhard Hoffmann, and Craig R. Rayner and the Activation Is Inhibited by Antiplatelet Agent Clopidogrel” Downloaded from Response to Comments on “Anti-Influenza Prodrug Deshi Shi, Jian Yang, Dongfang Yang, 424 Oseltamivir Is Activated by Carboxylesterase Human Edward L. LeCluyse, Chris Black, Li You, Carboxylesterase 1, and the Activation Is Inhibited by Fatemeh Akhlaghi, and Bingfang Yan Antiplatelet Agent Clopidogrel” jpet.aspetjournals.org at ASPET Journals on September 23, 2021

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

About the cover: Pharmacologically induced senescence. See the article by Coates et al. on page 70 of this issue.