The Journal of PHARMACOLOGY

And Experimental Therapeutics

A Publication of the American Society for Pharmacology and Experimental Therapeutics

January 2007 Vol. 320, No. 1 Contents

PERSPECTIVES IN PHARMACOLOGY and Classical Concepts of Quantitative Jonathan D. Urban, William P. Clarke, 1 Pharmacology Mark von Zastrow, David E. Nichols, Brian Kobilka, Harel Weinstein, Jonathan A. Javitch, Bryan L. Roth, Downloaded from Arthur Christopoulos Patrick M. Sexton, Keith J. Miller, Michael Spedding, and Richard B. Mailman

BEHAVIORAL PHARMACOLOGY

Inflammation-Induced Reduction of Spontaneous Activity by David J. Matson, Daniel C. Broom, 194 jpet.aspetjournals.org Adjuvant: A Novel Model to Study the Effect of Analgesics in Susan R. Carson, James Baldassari, Rats John Kehne, and Daniel N. Cortright Effects of Salvinorin A, a ␬-Opioid Hallucinogen, on a Eduardo R. Butelman, Marek Mandau, 300 Neuroendocrine Biomarker Assay in Nonhuman Primates Kevin Tidgewell, Thomas E. Prisinzano, with High ␬-Receptor Homology to Humans Vadim Yuferov, and Mary Jeanne Kreek Sex Differences in Steroid Modulation of Ethanol Withdrawal P. E. Alele and L. L. Devaud 427

in Male and Female Rats at ASPET Journals on September 30, 2021 WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-Octahydro-7bH- Karen L. Marquis, Annmarie L. Sabb, 486 cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]: A Novel 5- Sheree F. Logue, Julie A. Brennan, Hydroxytryptamine 2C Receptor-Selective Agonist with Michael J. Piesla, Tom A. Comery, Preclinical Antipsychotic-Like Activity Steven M. Grauer, Charles R. Ashby Jr., Huy Q. Nguyen, Lee A. Dawson, James E. Barrett, Gary Stack, Herbert Y. Meltzer, Boyd L. Harrison, and Sharon Rosenzweig-Lipson

CARDIOVASCULAR

Distinct KATP Channels Mediate the Antihypertrophic Effects Ying Xia, Sabzali Javadov, Tracey X. Gan, 14 of Activation in Neonatal Rat Ventricular Theresa Pang, Michael A. Cook, and Myocytes Morris Karmazyn Novel Rho Kinase Inhibitors with Anti-inflammatory and Chris Doe, Ross Bentley, David J. Behm, 89 Vasodilatory Activities Robert Lafferty, Robert Stavenger, David Jung, Mark Bamford, Terry Panchal, Eugene Grygielko, Lois L. Wright, Gary K. Smith, Zunxuan Chen, Christine Webb, Sanjay Khandekar, Tracey Yi, Robert Kirkpatrick, Edward Dul, Larry Jolivette, Joseph P. Marino, Jr., Robert Willette, Dennis Lee, and Erding Hu

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. Licofelone, a Balanced Inhibitor of Cyclooxygenase and 5- Cristina Vidal, Almudena Go´mez-Herna´ndez, 108 Lipoxygenase, Reduces Inflammation in a Rabbit Model of Eva Sa´nchez-Gala´n, Alejandro Gonza´lez, Atherosclerosis Luis Ortega, Juan Antonio Go´mez-Gerique, Jose´Tun˜o´n, and Jesu´s Egido Cyclooxygenase, p38 Mitogen-Activated Protein Kinase Keshari Thakali, Lauren Davenport, 236 (MAPK), Extracellular Signal-Regulated Kinase MAPK, Rho Gregory D. Fink, and Stephanie W. Watts Kinase, and Src Mediate Hydrogen Peroxide-Induced Contraction of Rat Thoracic Aorta and Vena Cava The Nitric Oxide-Donating Pravastatin Derivative, NCX 6550 G. Dever, C. M. Spickett, S. Kennedy, 419 [(1S-[1␣(␤S*,␦S*),2␣,6␣,8␤-(R*),8a␣ ]]-1,2,6,7,8,8a- C. Rush, G. Tennant, A. Monopoli, and Hexahydro-␤,␦,6-trihydroxy-2-methyl-8-(2-methyl-1- C. L. Wainwright oxobutoxy)-1-naphtalene-heptanoic Acid 4-(Nitrooxy)butyl Ester)], Reduces Splenocyte Adhesion and Reactive Oxygen Species Generation in Normal and Atherosclerotic Mice

CELLULAR AND MOLECULAR Comparative Studies of Anthraquinone- and Anthracene- Lihua Jin, Hiromi Sugiyama, 47 Tetraamines as Blockers of N-Methyl-D-aspartate Receptors Miki Takigawa, Daisuke Katagiri, Hideyuki Tomitori, Kazuhiro Nishimura, Navneet Kaur, Otto Phanstiel IV, Mariko Kitajima, Hiromitsu Takayama, Downloaded from Tadashi Okawara, Keith Williams, Keiko Kashiwagi, and Kazuei Igarashi Complete Inhibition of P-glycoprotein by Simultaneous Katalin Goda, Ferenc Fenyvesi, Zsolt Bacso´, 81 Treatment with a Distinct Class of Modulators and the UIC2 Henrietta Nagy, Tere´z Ma´ria´n, Attila Megyeri, Monoclonal Antibody Zolta´n Krasznai, Istva´n Juha´sz, Miklo´s Vecsernye´s, and Ga´bor Szabo´, Jr. jpet.aspetjournals.org A Comparison of the Antagonist Affinities for the Gi- and Jillian G. Baker and Stephen J. Hill 218 Gs-Coupled States of the Human Adenosine A1-Receptor

Mechanisms Linking Adenosine A1 Receptors and S. Husain, T. W. Shearer, and C. E. Crosson 258 Extracellular Signal-Regulated Kinase 1/2 Activation in Human Trabecular Meshwork Cells Comparison of Signaling Pathways Activated by the Relaxin Family Michelle L. Halls, Ross A. D. Bathgate, and 281 Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes Roger J. Summers at ASPET Journals on September 30, 2021 Inhibition of Human Preadipocyte Proteasomal Activity by Sandra De Barros, Alexia Zakaroff-Girard, 291 HIV Protease Inhibitors or Specific Inhibitor Lactacystin Max Lafontan, Jean Galitzky, and Leads to a Defect in Adipogenesis, Which Involves Matrix Virginie Bourlier Metalloproteinase-9 Ca2؉-Calmodulin and Janus Kinase 2 Are Required for Justin H. Turner, Maria N. Garnovskaya, 314

Activation of Sodium-Proton Exchange by the Gi-Coupled Sonya D. Coaxum, Tamara M. Vlasova, 5-Hydroxytryptamine1a Receptor Margarita Yakutovich, David M. Lefler, and John R. Raymond Lack of the Aryl Hydrocarbon Receptor Leads to Impaired Ran Wu, Li Zhang, Martin S. Hoagland, and 448 Activation of AKT/Protein Kinase B and Enhanced Sensitivity Hollie I. Swanson to Apoptosis Induced via the Intrinsic Pathway

ENDOCRINE AND DIABETES Desoxyrhaponticin (3,5-Dihydroxy-4-methoxystilbene 3-O-␤- Jian Mei Li, Chun Tao Che, 38 D-glucoside) Inhibits Glucose Uptake in the Intestine and Clara B. S. Lau, Po Sing Leung, and Kidney: In Vitro and in Vivo Studies Christopher H. K. Cheng Sergliflozin, a Novel Selective Inhibitor of Low-Affinity Kenji Katsuno, Yoshikazu Fujimori, 323 Sodium Glucose Cotransporter (SGLT2), Validates the Yukiko Takemura, Masahiro Hiratochi, Critical Role of SGLT2 in Renal Glucose Reabsorption and Fumiaki Itoh, Yoshimitsu Komatsu, Modulates Plasma Glucose Level Hideki Fujikura, and Masayuki Isaji Nicotinamide Reverses Neurological and Neurovascular M. J. Stevens, F. Li, V. R. Drel, 458 Deficits in Streptozotocin Diabetic Rats O. I. Abatan, H. Kim, D. Burnett, D. Larkin, and I. G. Obrosova The Thyroid Disruptor 1,1,1-Trichloro-2,2-Bis(p- Mario Rossi, Antonio Dimida, 465 Chlorophenyl)Ethane Appears to Be an Uncompetitive Inverse Maria Teresa Dell’anno, Agonist for the Maria Letizia Trincavelli, Patrizia Agretti, Franco Giorgi, Giovanni U. Corsini, Aldo Pinchera, Paolo Vitti, Massimo Tonacchera, and Roberto Maggio

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL The Prevention of Colitis by E Prostanoid Receptor 4 Agonist Guang-Liang Jiang, Amelia Nieves, 22 through Enhancement of Epithelium Survival and Wha Bin Im, David W. Old, Danny T. Dinh, Regeneration and Larry Wheeler The Extracellular cAMP-Adenosine Pathway Significantly Edwin K. Jackson, Zaichuan Mi, and 117 Contributes to the in Vivo Production of Adenosine Raghvendra K. Dubey The Nuclear Receptor Constitutively Active/Androstane Eric S. Tien, Kenji Matsui, Rick Moore, and 307 Receptor Regulates Type 1 Deiodinase and Thyroid Hormone Masahiko Negishi Activity in the Regenerating Mouse Liver

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA A p38␣ Selective Mitogen-Activated Protein Kinase Inhibitor Keith L. Kirkwood, Fei Li, Jill E. Rogers, 56 Prevents Periodontal Bone Loss Jodie Otremba, Derek D. Coatney, Jaclynn M. Kreider, Nisha J. D’Silva, Sarvajit Chakravarty, Sundeep Dugar, Linda S. Higgins, Andrew A. Protter, and Satyanarayana Medicherla

Agonist and Antagonist Effects of 15R-Prostaglandin (PG) D2 Chantal Cossette, Sinead E. Walsh, 173 and 11-Methylene-PGD2 on Human Eosinophils and Basophils Seongjin Kim, Gue-Jae Lee, John A. Lawson, Sophie Bellone, Joshua Rokach, and William S. Powell

METABOLISM, TRANSPORT, AND PHARMACOGENOMICS The Contribution of Intestinal UDP-Glucuronosyltransferases Melanie N. Tallman, Kristini K. Miles, 29

in Modulating 7-Ethyl-10-hydroxy-camptothecin (SN-38)- Fay K. Kessler, Judith N. Nielsen, Downloaded from Induced Gastrointestinal Toxicity in Rats Xianbin Tian, Joseph K. Ritter, and Philip C. Smith Relative Activation of Human Pregnane X Receptor versus Stephanie R. Faucette, Tong-Cun Zhang, 72 Constitutive Androstane Receptor Defines Distinct Classes of Rick Moore, Tatsuya Sueyoshi, CYP2B6 and CYP3A4 Inducers Curtis J. Omiecinski, Edward L. LeCluyse, Masahiko Negishi, and Hongbing Wang jpet.aspetjournals.org ␣ ␤ Marked Strain Differences in the Pharmacokinetics of an 4 1 Takashi Ito, Masayuki Takahashi, 124 Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)ureido]- Kenichi Sudo, and Yuichi Sugiyama phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism Bias in Estimation of Transporter Kinetic Parameters from Anand Balakrishnan, Naissan Hussainzada, 133 Overexpression Systems: Interplay of Transporter Expression Pablo Gonzalez, Marival Bermejo, Level and Substrate Affinity Peter W. Swaan, and James E. Polli at ASPET Journals on September 30, 2021

□S Concentration-Dependent Mode of Interaction of Angiotensin Takashi Iwanaga, Masanobu Sato, 211 II Receptor Blockers with Uric Acid Transporter Tomoji Maeda, Toshio Ogihara, and Ikumi Tamai Interaction of Nonsteroidal Anti-Inflammatory Drugs with Azza A. K. El-Sheikh, 229 Multidrug Resistance Protein (MRP) 2/ABCC2- and MRP4/ Jeroen J. M. W. van den Heuvel, ABCC4-Mediated Methotrexate Transport Jan B. Koenderink, and Frans G. M. Russel

□S Identification and Functional Analysis of Common Human Sevasti B. Koukouritaki, Mark T. Poch, 266 Flavin-Containing Monooxygenase 3 Genetic Variants Marilyn C. Henderson, Lisbeth K. Siddens, Sharon K. Krueger, Jonathan E. VanDyke, David E. Williams, Nicholas M. Pajewski, Tao Wang, and Ronald N. Hines Valproic Acid Is Not a Substrate for P-glycoprotein or Steffen Baltes, Maren Fedrowitz, 331 Multidrug Resistance Proteins 1 and 2 in a Number of in Carlos Luna Torto´s, Heidrun Potschka, and Vitro and in Vivo Transport Assays Wolfgang Lo¨scher Transport, Metabolism, and in Vivo Population Ahmed A. Othman, Shariq A. Syed, 344 Pharmacokinetics of the Chloro Benztropine Analogs, a Class Amy H. Newman, and Natalie D. Eddington of Compounds Extensively Evaluated in Animal Models of Drug Abuse

NEUROPHARMACOLOGY

Cannabinoid (CB1) Receptor Activation Inhibits Simon Akerman, Philip R. Holland, and 64 Trigeminovascular Peter J. Goadsby A Chimeric Human/Murine Anticocaine Monoclonal Antibody Andrew B. Norman, Michael R. Tabet, 145 Inhibits the Distribution of Cocaine to the Brain in Mice Mantana K. Norman, William R. Buesing, Amadeo J. Pesce, and William J. Ball Anticonvulsants for Nerve Agent-Induced Seizures: The Tsung-Ming Shih, Tami C. Rowland, and 154 Influence of the Therapeutic Dose of Atropine John H. McDonough 4-Aminopyridine Prevents the Conformational Changes Thomas W. Claydon, Moni Vaid, 162 Associated with P/C-Type Inactivation in Shaker Channels Saman Rezazadeh, Steven J. Kehl, and David Fedida Extended Access to Nicotine Self-Administration Leads to Laura E. O’Dell, Scott A. Chen, 180 Dependence: Circadian Measures, Withdrawal Measures, and Ron T. Smith, Sheila E. Specio, Extinction Behavior in Rats Robert L. Balster, Neil E. Paterson, Athina Markou, Eric P. Zorrilla, and George F. Koob Protein Kinase A Activation Down-Regulates, Whereas Gianfrancesco Cormaci, Tomohisa Mori, 202 Extracellular Signal-Regulated Kinase Activation Up-Regulates Teruo Hayashi, and Tsung-Ping Su ␴-1 Receptors in B-104 Cells: Implication for Neuroplasticity Nicotinic Regulation of Calcium/Calmodulin-Dependent M. I. Damaj 244 Protein Kinase II Activation in the Spinal Cord Inhibition of Nicotine Metabolism by Methoxysalen: M. I. Damaj, E. C. K. Siu, E. M. Sellers, 250 Pharmacokinetic and Pharmacological Studies in Mice R. F. Tyndale, and B. R. Martin Use-Dependent Block by Lidocaine but Not Is Andreas Leffler, Anne Reiprich, 354 More Pronounced in Tetrodotoxin (TTX)-Resistant Nav1.8 Durga P. Mohapatra, and Carla Nau Than in TTX-Sensitive Na؉ Channels BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, X. Ligneau, D. Perrin, L. Landais, 365 Hydrochloride], a Nonimidazole Inverse Agonist/Antagonist at J.-C. Camelin, T. P. G. Calmels,

the Human H3 Receptor: Preclinical Pharmacology I. Berrebi-Bertrand, J.-M. Lecomte, R. Parmentier, C. Anaclet, J.-S. Lin, V. Bertaina-Anglade, C. Drieu la Rochelle,

F. d’Aniello, A. Rouleau, F. Gbahou, Downloaded from J.-M. Arrang, C. R. Ganellin, H. Stark, W. Schunack, and J.-C. Schwartz

D2-Like Receptors Depolarize Dorsal Raphe Teresa K. Aman, Roh-Yu Shen, and 376 Neurons through the Activation of Nonselective Samir Haj-Dahmane Cationic Conductance ,The Experimental Alzheimer’s Disease Drug Posiphen [(؉)- Debomoy K. Lahiri, DeMao Chen

386 jpet.aspetjournals.org Phenserine] Lowers Amyloid-␤ Peptide Levels in Cell Culture Bryan Maloney, Harold W. Holloway, and Mice Qian-sheng Yu, Tada Utsuki, Tony Giordano, Kumar Sambamurti, and Nigel H. Greig Selective Activation of Group III Metabotropic Glutamate Anthony C. Vernon, Virginia Zbarsky, 397 Receptors by L-(؉)-2-Amino-4-phosphonobutryic Acid Krishna P. Datla, David T. Dexter, and Protects the Nigrostriatal System against 6-Hydroxydopamine Martin J. Croucher Toxicity in Vivo Two Protein Trafficking Processes at Motor Nerve Endings Gary Lawrence, Jiafu Wang, 410 at ASPET Journals on September 30, 2021 Unveiled by Botulinum Neurotoxin E C. K. N. Kwo Chion, K. Roger Aoki, and J. Oliver Dolly Group III Metabotropic Agonists Selectively Ce Zhang and Gerard J. Marek 437 Suppress Excitatory Synaptic Currents in the Rat Prefrontal

Cortex Induced by 5-Hydroxytryptamine2A Receptor Activation Pharmacologic Characterization of the Cloned Human Trace David B. Wainscott, Sheila P. Little, 475 Amine-Associated Receptor1 (TAAR1) and Evidence for Tinggui Yin, Yuan Tu, Vincent P. Rocco, Species Differences with the Rat TAAR1 John X. He, and David L. Nelson TOXICOLOGY Comparison of S-Adenosyl-L-methionine and N-Acetylcysteine Marcus V. Terneus, K. Kelley Kiningham, 99 Protective Effects on Acetaminophen Hepatic Toxicity A. Betts Carpenter, Sarah B. Sullivan, and Monica A. Valentovic Roles of , Free Fatty Acids, Thyroid Status, Jon E. Sprague, Xianmei Yang, 274 and Skeletal Muscle Uncoupling Protein 3 Expression in Joni Sommers, Tracy L. Gilman, and Sympathomimetic-Induced Thermogenesis Edward M. Mills ERRATUM Correction to “In Vitro Metabolism of (Nitroxy)butyl Ester 497 Nitric Oxide-Releasing Compounds: Comparison with Glyceryl Trinitrate” Correction to “NAP Enhances Neurodevelopment of Newborn 498 E-Deficient Mice Subjected to Hypoxia”

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

About the cover: Illustration of potential dimer arrangements and molecular model representations of the proposed dimer interfaces and effects of disulfide trapping of the respective interfaces on receptor activation. See the article by Urban et al. on page 1 of this issue.