PharmacologyMolecular

A Publication of the American Society for

Pharmacology and Experimental Therapeutics

Volume 73 ■ Number 6 ■ June 2008 ■ ISSN 0026-895X

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MOLECULAR PHARMACOLOGYA Publication of the American Society for Pharmacology and Experimental Therapeutics

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PERSPECTIVESMaking the T-Type Even Tinier: Corticotropin-Releasing Factor-Mediated Inhibition of Low-Voltage–

Activated Calcium Channel ActivityDiego L. Varela, Tamara Hermosilla, and Gerald W. Zamponi 1589

Refining Insights into High-Affinity Drug Binding to the Human Ether-a-go-go-Related GenePotassium ChannelJules C. Hancox and Andrew F. James 1592

ARTICLES

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Activation of Corticotropin-Releasing Factor Receptor 1 Selectively Inhibits CaV3.2 T-Type CalciumChannelsJin Tao, Michael E. Hildebrand, Ping Liao, Mui Cheng Liang, Gregory Tan, Shengnan Li,Terrance P. Snutch, and Tuck Wah Soong 1596

□S Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related (GITR)-Fc Fusion Protein InhibitsGITR Triggering and Protects from the Inflammatory Response after Spinal Cord InjuryGiuseppe Nocentini, Salvatore Cuzzocrea, Tiziana Genovese, Rodolfo Bianchini, Emanuela Mazzon,Simona Ronchetti, Emanuela Esposito, Di Paola Rosanna, Placido Bramanti, and Carlo Riccardi 1610

Protease-Activated Receptor-1 Mediates Thrombin-Induced Persistent Sodium Current in HumanCardiomyocytesCaroline Pinet, Vincent Algalarrondo, Sylvie Sablayrolles, Bruno Le Grand, Christophe Pignier,Didier Cussac, Michel Perez, Stephane N. Hatem, and Alain Coulombe 1622

Combined Targeting of Epidermal Growth Factor Receptor, Signal Transducer and Activator ofTranscription-3, and Bcl-XL Enhances Antitumor Effects in Squamous Cell Carcinoma of the Headand NeckAmanda L. Boehm, Malabika Sen, Raja Seethala, William E. Gooding, Maria Freilino,Silvia Man Yan Wong, Shaomeng Wang, Daniel E. Johnson, and Jennifer Rubin Grandis 1632

□S

Topological Mapping of the Asymmetric Drug Binding to the Human Ether-a-go-go–Related GeneProduct (HERG) Potassium Channel by Use of Tandem DimersToshihiko Myokai, Sunghi Ryu, Hirofumi Shimizu, and Shigetoshi Oiki 1643

MOLECULARPHARMACOLOGY

June 2008 Volume 73 Number 6 http://molpharm.aspetjournals.org ISSN 0026-895X

The and symbols in the table of contents identify articles discussed in the Perspectives.

Molecular Pharmacology (ISSN 0026-895X) is published monthly(two volumes per year beginning in January and July) by the Amer-ican Society for Pharmacology and Experimental Therapeutics, 9650Rockville Pike, Bethesda, MD 20814-3995; e-mail: info@aspet.org;Web site: http://www.aspet.org. Periodicals postage paid at Bethesda,MD and at additional mailing offices. POSTMASTER: Send addresschanges to Molecular Pharmacology, 9650 Rockville Pike, Bethesda,MD 20814-3995. Subscription rates: U.S.: $647.00 for institutionsand $264.00 for non-ASPET members. Outside the U.S.: $734.00for institutions and $351.00 for non-ASPET members. Single copy:

$59.00. GST Tax Number for Canadian subscribers: BN:13489 2330RT. Indexed or abstracted by Biochemistry & Biophysics CitationIndex®, Biological Abstracts, BIOSIS Previews Database, CurrentAwareness in Biological Sciences, Current Contents®/Life Sciences,EMBASE/Excerpta Medica, Index Medicus, Medical DocumentationService®, Reference Update®, Research Alert®, Science CitationIndex®, SciSearch®, and SIIC Data Bases. Copyright © 2008 by theAmerican Society for Pharmacology and Experimental Therapeutics.All rights reserved. Printed in the U.S.A.

The Nuclear Factor-�B Pathway Regulates Cytochrome P450 3A4 Protein StabilityR. C. Zangar, N. Bollinger, S. Verma, N. J. Karin, and Y. Lu 1652

A Role for Leu118 of Loop E in Agonist Binding to the �7 Nicotinic Acetylcholine ReceptorShiva Amiri, Masaru Shimomura, Ranjit Vijayan, Hisashi Nishiwaki, Miki Akamatsu,Kazuhiko Matsuda, Andrew K. Jones, Mark S. P. Sansom, Philip C. Biggin, and David B. Sattelle 1659

□S Multipathway Model Enables Prediction of Kinase Inhibitor Cross-Talk Effects on Migration of Her2-Overexpressing Mammary Epithelial CellsNeil Kumar, Raffi Afeyan, Hyung-Do Kim, and Douglas A. Lauffenburger 1668

Inhibition of c-Myc Down-Regulation by Sustained Extracellular Signal-Regulated Kinase ActivationPrevents the Antimetabolite Methotrexate- and Gemcitabine-Induced Differentiation in Non–Small-Cell Lung Cancer CellsJordi M. Serra, Antonio Gutierrez, Regina Alemany, Marıa Navarro, Teresa Ros, Carlos Saus,Jordi Gines, Antonia Sampol, Juan Carlos Amat, Lorenzo Serra-Moises, Javier Martın,Antonio Galmes, Oliver Vogler, and Joan Besalduch 1679

A cAMP-Dependent, Protein Kinase A-Independent Signaling Pathway Mediating Neuritogenesisthrough Egr1 in PC12 CellsAurelia Ravni, David Vaudry, Matthew J. Gerdin, Maribeth V. Eiden, Anthony Falluel-Morel,Bruno J. Gonzalez, Hubert Vaudry, and Lee E. Eiden 1688

Probing the Binding Sites and Mechanisms of Action of Two Human Ether-a-go-go-Related GeneChannel Activators, 1,3-bis-(2-Hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and 2-[2-(3,4-Dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD307243)Xulin Xu, Maurizio Recanatini, Marinella Roberti, and Gea-Ny Tseng 1709

Primary Peripheral T Cells Become Susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-MediatedApoptosis in Vitro upon Activation and in the Presence of Dendritic CellsNarendra P. Singh, Mitzi Nagarkatti, and Prakash Nagarkatti 1722

Me-Talnetant and Osanetant Interact within Overlapping but Not Identical Binding Pockets in theHuman Tachykinin Neurokinin 3 Receptor Transmembrane DomainsPari Malherbe, Caterina Bissantz, Anne Marcuz, Claudia Kratzeisen, Marie-Therese Zenner,Joseph G. Wettstein, Hasane Ratni, Claus Riemer, and Will Spooren 1736

□S Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene ExpressionMelissa A. Kramer, Allan E. Rettie, Mark J. Rieder, Erwin T. Cabacungan, and Ronald N. Hines 1751

Identification of the Xenobiotic-Metabolizing Enzyme Arylamine N-Acetyltransferase 1 as a NewTarget of Cisplatin in Breast Cancer Cells: Molecular and Cellular Mechanisms of InhibitionNilusha Ragunathan, Julien Dairou, Benjamin Pluvinage, Marta Martins, Emile Petit,Nathalie Janel, Jean-Marie Dupret, and Fernando Rodrigues-Lima 1761

Covalent Binding of the Nitroso Metabolite of Sulfamethoxazole Is Important in Induction of Drug-Specific T-Cell Responses in VivoLinling Cheng, Benjamin J. Stewart, Qiang You, Dennis R. Petersen, Joseph A. Ware,Joseph R. Piccotti, Thomas T. Kawabata, and Cynthia Ju 1769

Potent, Selective and Cell Penetrant Inhibitors of SF-1 by Functional Ultra-High-ThroughputScreeningFranck Madoux, Xiaolin Li, Peter Chase, Gina Zastrow, Michael D. Cameron,Juliana J. Conkright, Patrick R. Griffin, Scott Thacher, and Peter Hodder 1776

Kavalactones Protect Neural Cells against Amyloid � Peptide-Induced Neurotoxicity via ExtracellularSignal-Regulated Kinase 1/2-Dependent Nuclear Factor Erythroid 2-Related Factor 2 ActivationChristoph J. Wruck, Mario E. Gotz, Thomas Herdegen, Deike Varoga, Lars-Ove Brandenburg, andThomas Pufe 1785

Partial Deletion of the Nicotinic Cholinergic Receptor �4 or �2 Subunit Genes Changes theAcetylcholine Sensitivity of Receptor-Mediated 86Rb� Efflux in Cortex and Thalamus and AltersRelative Expression of �4 and �2 SubunitsCecilia Gotti, Milena Moretti, Natalie M. Meinerz, Francesco Clementi, Annalisa Gaimarri,Allan C. Collins, and Michael J. Marks 1796

Amiloride Derivatives and a Nonpeptidic Antagonist Bind at Two Distinct Allosteric Sites in theHuman Gonadotropin-Releasing Hormone ReceptorLaura H. Heitman, Kai Ye, Julia Oosterom, and Adriaan P. IJzerman 1808

Activation of Tyrosine Hydroxylase mRNA Translation by cAMP in Midbrain Dopaminergic NeuronsXiqun Chen, Lu Xu, Pheona Radcliffe, Baoyong Sun, and A. William Tank 1816

ATP Modulates Poly(ADP-Ribose) Polymerase-1-Facilitated Topoisomerase I-Linked DNA Religation inthe Presence of CamptothecinShin-Young Park, Chung-Hang Leung, and Yung-Chi Cheng 1829

Sazetidine-A Is a Potent and Selective Agonist at Native and Recombinant �4�2 NicotinicAcetylcholine ReceptorsRuud Zwart, Anna L. Carbone, Mirko Moroni, Isabel Bermudez, Adrian J. Mogg,Elizabeth A. Folly, Lisa M. Broad, Andrew C. Williams, Deyi Zhang, Chunjin Ding,Beverly A. Heinz, and Emanuele Sher 1838

□S Phenotype of the Cyp1a1/1a2/1b1(�/�) Triple-Knockout MouseNadine Dragin, Zhanquan Shi, Rajat Madan, Christopher L. Karp, Maureen A. Sartor, Chi Chen,Frank J. Gonzalez, and Daniel W. Nebert 1844

In Vivo Inhibition of Serine Protease Processing Requires a High Fractional Inhibition of Cathepsin CNathalie Methot, Daniel Guay, Joel Rubin, Diane Ethier, Karen Ortega, Simon Wong,Denis Normandin, Christian Beaulieu, T. Jagadeeswar Reddy, Denis Riendeau, andM. David Percival 1857

ERRATACorrection to “�2 Subunit Specificity of Cyclothiazide Inhibition on Glycine Receptors” 1866

Correction to Table of Contents (Volume 73, Number 4, April 2008) 1867

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

About the cover: Dock of ACh to wild-type �7 model (purple) overlaid onto the AChBP-carbamylcholine structure (1UV6, gray). Seethe article by Amiri et al. on page 1659 of this issue.

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