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The Journal of PHARMACOLOGY And Experimental Therapeutics A Publication of the American Society for Pharmacology and Experimental Therapeutics Vol 312, No. 3 March 2005 Contents O6OB%fl3K PERSPECTIVES IN PHARMACOLOGY Cannabinoid CBX Receptor Antagonists as PromisingOBIrtR New Bernard Le Foil and Steven R. Goldberg 875 Medications for Drug Dependence ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION Predictive Models of CYP3A4 Heteroactivation: In Vitro-in Vivo Ann-Charlotte Egtiell, J. Brian Houston, and Scaling and Pharmacophore Modeling C. Scott Boyer Immunogenicity and Rapid Blood Clearance of Liposomes Sean C. Semple, Troy O. Harasym, Kathy Containing Polyethylene Glycol-Lipid Conjugates and Nucleic A. Clow, Steven M. Ansell, Sandra K. Acid Klimuk, and Michael J. Hope 926 1020 Renal D-Amino Acid Oxidase Mediates Chiral Inversion of A^-Nitro-D-arginine Two Major Grapefruit Juice Components Differ in Time to Onset of Intestinal CYP3A4 Inhibition Yan-Fei Xin, Xiang-Jun Zhou, Xi Cheng, and Yong-Xiang Wang Mary F. Paine, Anne B. Criss, and Paul B. Watkins P-Glycoprotein and Mutlidrug Resistance-Associated Proteins Limit the Brain Uptake of Saquinavir in Mice Seonghee Park and Patrick J. Sinko 1249 Carrie K. Jones, Elizabeth Lutz Eberle, David B. Shaw, David L. McKinzie, and Harlan E. Shannon 1055 E. L. Lane, S. Cheetham, and P. Jenner 1124 Sharon Bingham, Paul J. Beswick, Chas Bountra, Terry Brown, Ian B. Campbell, Iain P. Chessell, Nick Clayton, Sue D. Collins, Philip T. Davey, Helen Goodland, Norman Gray, Claudine Haslam, Jonathan P. Hatcher, A. Jacqueline Hunter, Fiona Lucas, Graham Murkitt, Alan Naylor, Elizabeth Pickup, Becky Sargent, Scott G. Summerfield, Alexander Stevens, Sharon C. Stratton, and Joanne Wiseman 1161 BEHAVIORAL PHARMACOLOGY Pharmacologic Interactions between the Muscarinic Cholinergic and Dopaminergic Systems in the Modulation of Prepulse Inhibition in Rats Dopamine Uptake Inhibitor-Induced Rotation in 6Hydroxydopamine-Lesioned Rats Involves Both D, and D 2 Receptors but Is Modulated through 5-Hydroxytryptamine and Noradrenaline Receptors The Cyclooxygenase-2 Inhibitor GW406381X [2-(4EthoxyphenyI)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[l,5ijpyridazine] Is Effective in Animal Models of Neuropathic Pain and Central Sensitization Attenuation of Behavioral Effects of Cocaine by the Metabotropic Glutamate Receptor 5 Antagonist 2-MethyI-6(phenylethynyl)-pyridine in Squirrel Monkeys: Comparison with Dizocilpine Buyean Lee, Donna M. Platt, James K. Rowlett, Adepero S. Adewale, and Roger D. Spealman 1090 1151 1232 Self-Administration of Cocaine-Opioid Combinations by Rhesus Monkeys: Evaluation of the Role of jx Receptor Efficacy Using Labor Supply Analysis CARDIOVASCULAR Poly(ADP-Ribose) Polymerase Promotes Cardiac Remodeling, Contractile Failure, and Translocation of Apoptosis-Inducing Factor in a Murine Experimental Model of Aortic Banding and Heart Failure Cyclooxygenase-2 Inhibition Improves Vascular Endothelial Dysfunction in a Rat Model of Endotoxic Shock: Role of Inducible Nitric-Oxide Synthase and Oxidative Stress James K. Rowlett, Joshua S. Rodefer, and Roger D. Spealman 1289 Chun-Yang Xiao, Min Chen, Zsuzsanna Zsengeller, Hongshan Li, Levente Kiss, Mark Kollai, and Csaba Szabo 891 Agostino Virdis, Rocchina Colucci, Matteo Fornai, Corrado Blandizzi, Emiliano Duranti, Stefania Pinto, Nunzia Bernardini, Cristina Segnani, Luca Antonioli, Stefano Taddei, Antonio Salvetti, and Mario Del Tacca 945 Blood Clearance and Activity of Erythrocyte-Coupled Fibrinolytics Kumkum Ganguly, Tatiana Krasik, Sandra Medinilla. Khali! Bdeir, Douglas B. Cines, Vladimir R. Mnzykantov, and Juan Carlos Murciano 1106 The Effects of Tamoxifen and Its Metabolites on Platelet Function and Release of Reactive Oxygen Intermediates Olga Vitseva, David A. Flockhart, Yan Jin, Sonia Varghese, and Jane E. Freedman 1144 Epidermal Growth Factor Receptor-Dependent and Independent Pathways in Hydrogen Peroxide-Induced Mitogen-Activated Protein Kinase Activation in Cardiomyocytes and Heart Fibroblasts Sally Purdom and Qin M. Chen ] 179 Raloxifcne Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca 2+ Influx Yau-Chi Chan, Fung-Ping Leung, Xiaoqiang Yao, Chi-Wai Lau, Paul M. Vanhoutte, and Yu Huang 1266 Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction Raquel Binda Pereira, Carmem Luiza Sartorio, Daiton Valentim Vassallo, and Ivanita Slefanon 1321 A New ATP-Sensitive Potassium Channel Opener Reduces Blood Pressure and Reverses Cardiovascular Remodeling in Experimental Hypertension Hai Wang, Cbao-Liang Long, and Ying-Li Zhang 1326 CELLULAR AND MOLECULAR Green Tea PolyphenoMnduced Epidermal Keratinocyte Differentiation Is Associated with Coordinated Expression of p57/KIP2 and Caspase 14 Stephen Hsu, Tetsuya Yamamoto, James Borke, Douglas S. Walsh, Baldev Singh, Sushma Rao, Kamatani Takaaki, Nam Nah-Do, Carol Lapp, David Lapp, Emily Foster, Wendy B. Bollag, Jill Lewis, John Wataha, Tokio Osaki, and George Schuster 884 Induction of Nitric Oxide Production by the Cytostatic Macrolide Apicularen A [2,4-Heptadienamide, N-[{lE)-3[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14Dihydroxy-l-oxo5,9-epoxy-l//-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)] and Possible Role of Nitric Oxide in Apicularen A-Induced Apoptosis in RAW 264.7 Cells JangJa Hong, Aya Yokomakura, Yasuhiro Nakano, Hyun Seung Ban, Kenji Ishihara, Jong-Woong Ahn, OkPyo Zee, and Kazuo Ohuchi 968 Positional Isomerism Markedly Affects the Growth Inhibition of Colon Cancer Cells by Nitric Oxide-Donating Aspirin in Vitro and in Vivo Khosrow Kashfi, Simona Borgo, Jennie L. Williams, Jie Chen, Jianjun Gao, Athanasios Glekas, Francesca Benedini, Piero del Soldato, and Basil Rigas 978 In Vitro Metabolism of Nitric Oxide-Donating Aspirin: The Effect of Positional Isomerism Jianjun Gao, Khosrow Kashfi, and Basil Rigas 989 Angiotensin II-Induced Akt Activation through the Epidermal Growth Factor Receptor in Vascular Smooth Muscle Cells Is Mediated by Phospholipid Metabolites Derived by Activation of Phospholipase D Fang Li and Kafait U. Malik 1043 Evidence for Pleiotropic Signaling at the Mouse /3 3Adrcnoceptor Revealed by SR59230A [3-(2-Ethylphenoxy)-l-[(1 ,S)-1,2,3,4-tetrahy dronapth-1 -ylamino] -2S-2-propanol Oxalate] Dana S. Hutcbinson, Masaaki Salo, Bronwyn A. Evans, Arthur Christopoulos, and Roger J. Summers 1064 Phospholipase D Signaling and Extracellular Signal-Regulated Kinase-1 and -2 Phosphorylation (Activation) Are Required for Maximal Phorbol Ester-Induced Transglutaminase Activity, a Marker of Keratinocyte Differentiation Wendy B. Bollag, Xiaofeng Zhong. M. Ernest Dodd, David M. Hardy, Xiangjian Zheng, and W. Thomas AUred 1223 Protease Inhibitor Treatments Reveal Specific Involvement of Matrix MetaIloproteinase-9 in Human Adipocyte Differentiation CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY YC-1 [3-(5'-Hydroxymethyl-2'-furyl)-l-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G 0-Gi in Human Hepatocellular Carcinoma Cells GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL Effect of Neocuproine, a Copper(I) Chelator, on Rat Bladder Function Endogenous Interleukin-6 Enhances the Renal Injury, Dysfunction, and Inflammation Caused by Ischemia/Reperfusion INFLAMMATION AND IMMUNOPHARMACOLOGY Effect of E6060 [4-{5-[7-Fluoro-4{trifluoromethyl)benzo[/>]furan-2-yl]-l/^2-pyrrolyI}benzoic Acid], a Novel Subtype-Selective Retinoid, on Lupus-Like Nephritis in Female (NZBxNZW)Fl Mice Virginie Bourlier, Alexia Zakaroff-Girard, Sandra De Barms, Christophe Pizzacalla, Veronique Durand de Saint Front, Max Lafonlan, Anne Bouloumie, and Jean Galitzky Shih-Wei Wang, Shiow-Lin Pan, Jih-Hwa Guh, Hui-Iing Chen, DongMing Huang, Ya-Ling Chang, ShengChu Kuo. Fang-Yu Lee, and Che-Ming Teng 1272 917 Cemil Gocmen, Ben Giesselman, and William C. de Groat 1138 Nimesh S. A. Patel, Prabal K. Chatterjee, Rosanna Di Paola, Emanuela Mazzon, Domenico Britti, Angelina De Sarro, Salvalore Cuzzocrea, and Chris toph Thiemermann 1 170 Prostaglandin D2-Induced Eosinophilic Airway Inflammation Is Mediated by CRTH2 Receptor Toshihiko Yamauchi, Akira Ishibashi, Kohdoh Shikata, Naoki Tokuhara, Kenichiro Seine. Seiichi Kobayashi, and Mitsuo Nagai Yoshiki Shiraishi, Koichiro Asano, Takeshi Nakajima, Tsuyoshi Oguma, Yusuke Suzuki, Tctsuya Shiomi, Koichi Sayama, Kyoko Niimi, Misa Wakaki, Junko Kagyo, Eiji Ikeda, Hiroyuki Hirai, Kazuhiro Yamaguchi, and Akitoshi Ishizaka Ethyl Pyruvate Inhibits Nuclear Factor-KB-Dependent Signaling by Directly Targeting p65 Yusheng Han, Joshua A. Englert, Runkuan Yang, Russell L. Delude, and Mitchell P. Fink 1097 Glabridin, an Isoflavan from Licorice Root, Inhibits Inducible Nitric-Oxide Synthase Expression and Improves Survival of Mice in Experimental Model of Septic Shock Valdecoxib: Assessment of Cyclooxygenase-2 Potency and Selectivity Jong Soon Kang, Yeo Dae Yoon, Ig Jun Cho, Mi Hwa Han, Chang Woo Lee, Song-Kyu Park, and Hwan Mook Kim 1187 James K. Gierse, Yan Zhang, William F. Hood, Mark C. Walker, Jennifer S. Trigg, Timothy J. Maziasz, Carol M. Koboldt, Jerry L. Muhammad, Ben S. Zweifel, Jaime L. Masferrer, Peter C. Isakson, and Karen Seibcrt 1206 Cilostazol Prevents Remnant Lipoprotein Particle-Induced Monocyte Adhesion to Endothelial Cells by Suppression of Adhesion Molecules and Monocyte Chemoattractant Protein-1 Expression via Lectin-Like Receptor for Oxidized LowDensity Lipoprotein Receptor Activation So Youn Park, Jeong Hyun Lee, Yong Ki Kim, Chi Dae Kim, Byung Yong Rhim, Won Suk Lee, and Ki Whan Hong 1241 NEUROPHARMACOLOGY Differential Effects on Current Kinetics by Point Mutations in the lurcher Motif of NR1/NR2A Receptors Corticotropin-Releasing Factor Receptor 1 and Central Heart Rate Regulation in Mice during Expression of Conditioned Fear \s} Amiloride Peptide Conjugates: Prodrugs for Sodium-Proton Exchange Inhibition Mixed-Lineage Kinase Inhibitors Require the Activation of Trk Receptors to Maintain Long-Term Neuronal Trophism and Survival Dual, Hyperalgesic, and Analgesic Effects of the High-Efficacy 5-Hydroxytryptamine 1A (5-HT1A) Agonist F 13640 [(3Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2ylmethyl)-ainino]-methyl}piperidin-l-yl]methanone, Fumaric Acid Salt]: Relationship with 5-HT,A Receptor Occupancy and Kinetic Parameters 938 954 Bo Hu and Fang Zheng 899 Oliver Stiedl, Michael Meyer, Olaf Jahn, Sven Ove Ogren, and Joachim Spiess 905 Hasan Palandoken, Kolbot By, Manu Hegde, William R. Harley, Fredric A. Gorin, and Michael H. Nant? Leo H. Wang, Andrew J. Paden, and Eugene M. Johnson, Jr. 961 Laurent Bardin, Marie-Bernadette Assie, Marline Pelissou, Isabelle Royer-Urios, Adrian Newman-Tancredi, Jean-Paul Ribel, Francois Sautel, Wouter Koek, and Francis C. Colpaert 1007 1034 A Tyr-W-MIF-1 Analog Containing D-Pro2 Acts as a Selective jLt2-Opioid Receptor Antagonist in the Mouse Hiroyuki Watanabe, Daisuke Nakayama, Kanenori Ito, Chizuko Watanabe, Hirokazu Mizoguchi, Tsutomu Fujimura, Kimie Murayama, Shunsuke Kawamura, Takurai Sato, Chikai Sakurada, Tsukasa Sakurada, and Shinobu Sakurada 1075 Differential GABAit Receptor Modulation of Ethanol Effects on GABAA Synaptic Activity in Hippocampal CA1 Neurons [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a Highly Potent and Selective Agonist of the Nociceptin/Orphanin FQ Receptor Peter H. Wu, Wolfgang Poelchen, and William R. Proctor 1082 Giacomo Carra, Anna Rizzi, Remo Guerrini, Timothy A. Barnes, John McDonald, Christopher P. Hebbes, Flora Mela, Velga A. Kenigs, Giuliano Marzola, Daniela Rizzi, Elaine Gavioli, Silvia Zucchini, Domenico Regoli, Michele Morari, Severo Salvador!, David J. Rowbotham, David G. Lambert, Daniel R. Kapusta, and Girolamo Calo' Mayuko Oda, Norihito Kitagawa, Bang-Xiang Yang, Tadahide Totoki, and Masatoshi Morimoto 1114 Quantitative and Fiber-Selective Evaluation of DoseDependent Nerve Blockade by Intrathecal Lidocaine in Rats Memantine Blocks a7* Nicotinic Acetylcholine Receptors More Potently Than A'-Methyl-D-aspartate Receptors in Rat Hippocampal Neurons ; The Selective a7 Nicotinic Acetylcholine Receptor Agonist PNU-282987[A4(3tf)-l-Azabicyclo[2.2.2]oct-3-yl]-4chlorobenzamide Hydrochloride] Enhances GABAergic Synaptic Activity in Brain Slices and Restores Auditory Gating Deficits in Anesthetized Rats Differential Mechanisms of Antianalgesia Induced by Endomorphin-1 and Endomorphin~2 in the Ventral Periaqueductal Gray of the Rat Postnatal Inorganic Lead Exposure Reduces Midbrain Dopaminergic Impulse Flow and Decreases Dopamine Dl Receptor Sensitivity in Nucleus Accumbens Neurons Nicotinic Acetylcholine Receptor-Mediated [3H]Dopamine Release from Hippocampus Repeated Cocaine Administration Increases Membrane Excitability of Pyramidal Neurons in the Rat Medial Prefrontal Cortex Comparison of Peptidic and Nonpeptidic 5-Opioid Agonists on Guanoshie 5'-0-(3-[35S]thio)triphosphate ([35S]GTPyS) Binding in Brain Slices from Sprague-Dawley Rats TOXICOLOGY Protein Kinase C Signaling as a Survival Pathway against CYP2E1-Derived Oxidative Stress and Toxicity in HepG2 Cells Ciglitazone-Induced Lenticular Opacities in Rats: In Vivo and Whole Lens Explant Culture Evaluation ERRATUM Correction to "DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-lphenyl-1,3,8-triazaspiro[4,5]dec-3-yI]-acetic Acid), a Novel, Systematically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: II. In Vivo Pharmacological Characterization in the Rat" 1132 Yasco Aracava, Edna F. R, Pereira, Alfred Maelicke, and Edson X. Albuquerque 1195 M. Hajos, R. S. Hurst, W. E. Hoffmann, M. Krause, T. M. Wall, N. R. Higdon, and V. E. Groppi 1213 MaiaTerashvili, Hsiang-en Wu, Randy J. Leitermann, Han-Sen Sun, Andrew D. Clithero, and Leon F. Tseng 1257 Mahboubeh Tavakoli-Nezhad and David K. Pitts 1280 Ying-Jun Cao, Carol S. Surowy, and Pamela S. Puttfarcken 1298 Fernando J. Nasif, Kyriaki Sidiropoulou, Xiu-Ti Hu, and Francis J. White 1305 Emily M. Julkiewicz, Nicholas P. Walker, John E. Folk, Kenner C. Rice, Philip S. Portoghese, James H. Woods, and John R. Traynor 1314 Jose M. Jimenez-Lopez and Arthur I. Cederbaum 998 Michael D. Aleo, Colleen M. Doshna, and Kimberly A. Navetta 1027 Garth T. Whiteside, James E. Harrison, Michelle S. Pearson, Zhengming Chen, Paul I. Turchin, James D. Pomonis, Lilly Mark, Katharine Walker, and Kevin C. Brogle 1334