MOLECULAR PHARMACOLOGY ______________________________________ September 2004 Volume 66 Number 3 http://molpharm.aspetjournals.org ISSN 0026-895X PERSPECTIVE Arrestin-Independent Internalization of G Protein-Coupled Receptors M Chris J. van Koppen and Karl H. Jakobs 365 ARTICLES COX-2 Regulates the Insulin-Like Growth Factor I-Induced Potentiation of Zn 3+-Toxicity in Primary Cortical Culture Joo-Young Im, Doyeun Kim, Kang-Woo Lee, Jung-Bin Kim, Ja-Kyeong Lee, Dong Sik Kim, Young Ik Lee, Kwon-Soo Ha, Cheol O Joe, and Pyung-Lim Han 368 Agonist-Induced Internalization of Leukotriene B 4 Receptor 1 Requires G-Protein-Coupled Receptor Kinase 2 but Not Arrestins Zhangguo Chen, Remi Gaudreau, Christian Le Gouill, Marek Rola-Pleszczynski. and Jana Stankovd 377 Rapid Regulation of P-Glycoprotein at the Blood-Brain Barrier by Endothelin-1 Anika M. S. Hartz, Bjbrn Bauer, Gert Fricker, and David S. Miller 387 Regulation of the Stability of P-Glycoprotein by Ubiquitination Zhigang Zhang, Jin-Ying Wu, William N. Halt, and Jin-Ming Yang 395 Antisense Evidence for Nuclear Factor-tcB-Dependent Embryopathies Initiated by Phenytoin-Enhanced Oxidative Stress Julia C. Kennedy, Sylvie Memet, and Peter G. Wells 404 Pregnane X Receptor Up-Regxilation of P-Glycoprotein Expression and Transport Function at the Blood-Brain Barrier Bjb'rn Bauer, Anika M. S, Hartz, Gert Fricker, and David S. Miller 413 The al Nicotinic Acetylcholine Receptor Subunit Exists in Two Isoforms that Contribute to Functional Ligand-Gated Ion Channels Emily G. Severance, Hongling Zhang, Yolmari Cruz, Sergei Pakhlevaniants, Stephen H. Hadley, Jahanshah Amin, Lynn Wecker, Crystal Reed, and Javier Cuevas 420 Mutation E522K in Human DNA Topoisomerase II/3 Confers Resistance to Methyl JV-(4'-(9acridinylamino)-phenyl)carbamate hydrochloride and Methyl A^-(4r-(9-acridinylamino)-3-methoxyphenyl) methane sulfonamide but Hypersensitivity to Etoposide Chrysoula Leontiou, Jeremy H. Lakey, and Caroline A. Austin 430 Enhancement of Fibronectin Fibrillogenesis and Bone Formation by Basic Fibroblast Growth Factor via Protein Kinase C-Dependent Pathway in Rat Osteoblasts Chih-Hsin Tang, Rong-Sen Yang, Tsang-Hai Huang, Shing-Hwa Liu, and Wen-Mei Fu 440 Prediction of in Vivo Biliary Clearance from the in Vitro Transcellular Transport of Organic Anions across a Double-Transfected Madin-Darby Canine Kidney II Monolayer Expressing Both Rat Organic Anion Transporting Polypeptide 4 and Multidrug Resistance Associated Protein 2 Makoto Sasaki, Hiroshi Suzuki, Jun Aoki, Kousei Ito, Peter J. Meier, and Yuichi Sugiyama 450 P-Glycoprotein Mediates Resistance to Histidine Kinase Inhibitors Sonia Arora, Jin-Ming Yang, Ryutaro Utsumi, Tadashi Okamoto, Takashi Kitayama, and William N. Rait 460 Activation and Inhibition of Neuronal G Protein-Gated Inwardly Rectifying K + Channels by P2Y Nucleotide Receptors Alexander K. Filippov, Jose M. Fernandez-Fernandez, Stephen J. Marsh, Joseph Simon, Eric A. Barnard, and David A. Brown 468 DNA Damage Induced by Temozolomide Signals to both ATM and ATR: Role of the Mis match Repair System Simona Caporali, Sabrina Falcinelli, Giuseppe Starace, Maria Teresa Russo, Enzo Bonmassar, Josef Jiricny, and Stefania DAtri 478 3-Morpholinylsydnonimine Inhibits Glutamatergic Transmission in Rat Rostral Ventrolateral Medulla via Peroxynitrite Formation and Adenosine Release Chiung-Chun Huang, Samuel H. H. Chan, and Kuei-Sen Hsu 492 2,3,7,8-Tetrachlorodibenzo-p-dioxin Blocks Androgen-Dependent Cell Proliferation of LNCaP Cells through Modulation of pRB Phosphorylation Sonya Barnes-Ellerbe, Karen E. Knudsen, and Alvaro Puga 502 2,3,7,8-Tetrachlorodibenzo-p-dioxin Activation of the Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Pathway Causes Developmental Toxicity through a CYP1A Independent Mechanism in Zebrafish Sara A. Carney, Richard E. Peterson, and Warren Heideman 512 Dissociation of [ 3H]L-Glutamate Uptake from L-Glutamate-Induced [3H]D-Aspartate release by 3Hydroxy-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-c?]isoxazole-4-carboxyric Acid and 3-Hydroxy-4,5,6,6atetrahydro-3ai/-pyrrolo[3,4-d]isoxazole-6-carboxylic Acid, Two Conformationally Constrained Aspartate and Glutamate Analogs Marcella Funicello, Paola Conti, Marco De Amid, Carlo De Micheli, Tiziana Mennini, and Marco Gobbi 522 The Two-Pore-Domain K + Channels TREK-1 and TASK-3 Are Differentially Modulated by Copper and Zinc Marco Gruss, Alistair Mathie, William R. Lieb, and Nicholas P. Franks 530 Cholinergic Drugs for Alzheimer's Disease Enhance in Vitro Dopamine Release Lifen Zhang, Fu-Ming Zhou, and John A. Dani 538 Key Differences in Molecular Complexes of the Cholecystokinin Receptor with Structurally Related Peptide Agonist, Partial Agonist, and Antagonist Sonnet J. H. Arlander, Maoqing Dong, Xi-Qin Ding, Delia I. Pinon, and Laurence J. Miller 545 Induction of Radiosensitization by Indolocarbazole Derivatives: The Role of DNA Topoisomerase I Allan Y. Chen, Skyh-Jen Shih, Michael Hsiao, Mace L. Rothenberg, and Michelle Prudhomme 553 YC-1-Induced Cyclooxygenase-2 Expression Is Mediated by cGMP-Dependent Activations of Ras, Phosphoinositide-3- OH-kinase, Akt, and Nuclear Factor-KB in Human Pulmonary Epithelial Cells Ming-Shyan Chang, Wen-Sen Lee, Bing-Chang Chen, Joen-Rong Sheu, and Chien-Huang Lin 561 Effects of Antisense Oligonucleotide-Mediated Depletion of Tumor Necrosis Factor (TNF) Receptor 1Associated Death Domain Protein on TNF-Induced Gene Expression Andrew M. Siwkowski, Lisa A. Madge, Seongjoon Koo, Erin L. McMillan, Brett P. Monia, Jordan S. Pober, and Brenda F. Baker 572 Low Concentrations of Vinflunine Induce Apoptosis in Human SK-N-SH Neuroblastoma Cells through a Postmitotic G± Arrest and a Mitochondrial Pathway Bertrand Pourroy, Manon Carre, Stephane Honore, Veronique Bourgarel-Eey, Anna Kruczynski, Claudette Briand, and Diane Braguer 580 Nordihydroguaiaretic Acid Does Not Disaggregate /3-Amyloid(l-40) Protofibrils but Does Inhibit Growth Arising from Direct Protofibril Association Melissa A. Moss, Nicholas H. Varvel, Michael R. Nichols, Dana Kim Reed, and Terrone L. Rosenberry 592 Identification of the P2Y12 Receptor in Nucleotide Inhibition of Exocytosis from Bovine Chromaffm Cells Steven J. Ennion, Andrew D. Powell, and Elizabeth P. Seward 601 Berberine Inhibits HIF-la Expression via Enhanced Proteolysis Shankung Lin, Shiow-Chwen Tsai, Chun-Chung Lee, Bao-Wei Wang, Jer-Young Liou, and Kou-Gi Shyu 612 Small Interfering RNA-Mediated Suppression of dUTPase Sensitizes Cancer Cell Lines to Thymidylate Synthase Inhibition Sara E. Koehler and Robert D. Ladner 620 DNA Topoisomerase I As One of the Cellular Targets of Certain Tyrphostin Derivatives Sarit Bendetz-Nezer, Aviv Gazit, and Esther Priel 627 A Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor Potentiates the Activity of the Conventional Chemotherapeutic Agents Paclitaxel and Doxorubicin in Tumor Xenograft Models Stuart Emanuel, Robert H. Gruninger, Angel Fuentes-Pesquera, Peter J. Connolly, Jennifer A, Seamon, Susan Hazel, Rose Tominovich, Beth Hollister, Cheryl Napier, Michael R. D'Andrea, Michael Reuman, Gilles Bignan, Robert Tuman, Dana Johnson, David Moffatt, Mark Batchelor, Anne Foley, James O'Connell, Rodger Allen, Martin Perry, Linda Jolliffe, and Steven A. Middleton 635 Lidocaine: A Foot in the Door of the Inner Vestibule Prevents Ultra-Slow Inactivation of a VoltageGated Sodium Channel Walter Sandtner, Julia Szendroedi, Touran Zarrabi, Eva Zebedin, Karlheinz Hilber, Ian Glaaser, Harry A. Fozzard, Samuel C. Dudley, and Hannes Todt 648 Regulation of Nicotinic Acetylcholine Receptor Channel Function by Acetylcholinesterase In hibitors in Rat Hippocampal CA1 Interneurons Dmitriy Fayuk and Jerrel L. Yakel 658 y-Mangostin Inhibits Inhibitor-KB Kinase Activity and Decreases Lipopolysaccharide-Induced Cyclooxygenase-2 Gene Expression in C6 Rat Glioma Cells Keigo Nakatani, Tohru Yamakuni, Nobuhiko Kondo, Tsutomu Arakawa, Kenji Oosawa, Susumu Shimura, Hiroyasu Inoue, and Yasushi Okizumi 667 Enantioselective Effects of Hydroxy Metabolites of Bupropion on Behavior and on Function of Monoamine Transporters and Nicotinic Receptors M. Imad Damaj, F. Ivy Carroll, J. Brek Eaton, Hernan A. Navarro, Bruce E. Blough, Sadiq Mirza, Ronald J. Lukas, and Billy R. Martin 675 Flavonoids Inhibit Tumor Necrosis Factor-a-Induced Up-Regulation of Intercellular Adhesion Molecule-1 (ICAM-1) in Respiratory Epithelial Cells through Activator Protein-1 and Nuclear Factor-KB: Structure-Activity Relationships Ching-Chow Chen, Man-Ping Chow, Wei-Chien Huang, Yi-Chu Lin, and Ya-Jen Chang 683 Role of Liver-Enriched Transcription Factors in the Down-Regulation of Organic Anion Transporting Polypeptide 4 (Oatp4; Oatplb2; Slc21alO) by Lipopolysaccharide Ning Li and Curtis D. Klaassen 694 Diethylstilbestrol Is a Potent Inhibitor of Store-Operated Channels and Capacitative Ca 2+ Influx Sergey I. Zakharov, Tarik Smani, Yuliya Dobrydneva, Francisco Monje, Craig Fichandler, Peter F. Blackmore, and Victoria M. Bolotina 702 The Myosin ATPase Inhibitor 2,3-Butanedione monoxime Dictates Transcriptional Activation of Ion Channels and Ca 2+ -Handling Proteins Jiirgen Borlak and Carotin Zwadlo 708 The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of l-Methyl-4- (2'-aminophenyl)-l,2,3,6-tetrahydropyridine (2'-NH2-MPTP) Adam L. Numis, Erica L. linger, Douglas L. Sheridan, Angela C. Chisnell, and Anne M. Andrews 718 Acetaminophen: A Central Analgesic Drug That Involves a Spinal Tropisetron-Sensitive, Non-5-HT 3 ReceptorMediated Effect F. Libert, J. Bonnefont, E. Bourinet, E, Doucet, A. Alloui, M. Hamon, J. Nargeot, and A. Eschalier 728 Evidence for a Novel K + Channel Modulated by a 1A-Adrenoceptors in Cardiac Myocytes Stephanie C. M, Choisy, Jules C. Hancox, Lesley A. Arberry, A. Martyn Reynolds, Michael J. Shattock, and Andrew F. James 735 Glutathione Depletion in CYP2El~Expressing Liver Cells Induces Toxicity Due to the Activation of p38 Mitogen-Activated Protein Kinase and Reduction of Nuclear Factor-KB DNA Binding Activity Defeng Wu and Arthur Cederbaum 749 Functional Role of a C-Terminal G/37-Binding Domain of Ca v2.2 Channels Bin Li, Huijun Zhong, Todd Scheuer, and William A. Catterall 761