PHARMACOLOGYPHARMACOLOGYThe Journal of

And Experimental Therapeutics

A Publication of the American Society for

Pharmacology and Experimental Therapeutics

Edited for the Society by Rick G. Schnellmann

Volume 326 ■ Number 1 ■ July 2008 ■ ISSN 0022-3565

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BEHAVIORAL PHARMACOLOGYAntipsychotic-Like Properties of Phosphodiesterase 4Inhibitors: Evaluation of 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724) with Auditory Event-RelatedPotentials and Prepulse Inhibition of Startle

T. B. Halene and S. J. Siegel 230

□S Neuroactive Steroid Stereospecificity of Ethanol-LikeDiscriminative Stimulus Effects in Monkeys

Kathleen A. Grant, Christa M. Helms,Laura S. M. Rogers, and Robert H. Purdy

354

CARDIOVASCULARCyclooxygenase-2-Linked Attenuation of Hypoxia-InducedPulmonary Hypertension and Intravascular Thrombosis

Mary-Clare Cathcart, Rasa Tamosiuniene,Gang Chen, Tomas G. Neilan,Aidan Bradford, Kenneth J. O’Byrne,Desmond J. Fitzgerald, andGraham P. Pidgeon

51

6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)quinolinone (Cilostazol), a Phosphodiesterase Type 3Inhibitor, Reduces Infarct Size via Activation ofMitochondrial Ca2�-Activated K� Channels in Rabbit Hearts

Mika Fukasawa, Hirofumi Nishida,Toshiaki Sato, Masaru Miyazaki, andHaruaki Nakaya

100

Cardioprotective Effect of Morphine and a Blocker ofGlycogen Synthase Kinase 3�, SB216763 [3-(2,4-Dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via Inhibition of the Mitochondrial PermeabilityTransition Pore

Fatou Nsoure Obame,Catherine Plin-Mercier, Rana Assaly,Roland Zini, Jean Luc Dubois-Rande,Alain Berdeaux, and Didier Morin

252

Simvastatin Inhibits Central Sympathetic Outflow in HeartFailure by a Nitric-Oxide Synthase Mechanism

Lie Gao, Wei Wang, and Irving H. Zucker 278

Hydrolysis of cis- and trans-Epoxyeicosatrienoic Acids by RatRed Blood Cells

Houli Jiang, Angela G. Zhu,Magdalena Mamczur, Christophe Morisseau,Bruce D. Hammock, John R. Falck, andJohn C. McGiff

330

CELLULAR AND MOLECULAR□S Induction of Apoptosis in Neurofibromatosis Type 1

Malignant Peripheral Nerve Sheath Tumor Cell Lines by aCombination of Novel Farnesyl Transferase Inhibitors andLovastatin

Jonathan W. Wojtkowiak, Farid Fouad,Daniel T. LaLonde, Miriam D. Kleinman,Richard A. Gibbs, John J. Reiners, Jr.,Richard F. Borch, andRaymond R. Mattingly

1

Kinin B2 Receptor-Mediated Bradykinin Internalization andMetalloendopeptidase EP24.15-Dependent IntracellularBradykinin Degradation

Caroline Sanden, Johan Enquist,Sara H. Bengtson, Heiko Herwald, andL. M. Fredrik Leeb-Lundberg

24

The Journal of

PHARMACOLOGYAnd Experimental Therapeutics

A Publication of the American Society for Pharmacology and Experimental Therapeutics

July 2008 Vol. 326, No. 1

Contents

The Journal of Pharmacology and Experimental Therapeutics (ISSN0022-3565) is published monthly by the American Society for Pharma-cology and Experimental Therapeutics, 9650 Rockville Pike,Bethesda, MD 20814-3995; email: info@aspet.org; web site:www.aspet.org. Periodicals postage paid at Bethesda, MD, and at addi-tional mailing offices. POSTMASTER: Send address changes to The Jour-nal of Pharmacology and Experimental Therapeutics, 9650 RockvillePike, Bethesda, MD 20814-3995. Subscription rates: U.S.: $893.00 forinstitutions and $389.00 for non-ASPET members. Outside the U.S.:$1,049.00 for institutions and $545.00 for non-ASPET members.

Single copy: $79.00. GST Tax Number for Canadian subscribers: BN:13489 2330 RT. Indexed or abstracted by Biochemistry & BiophysicsCitation Index®, Biological Abstracts, BIOSIS Previews Database, Bio-Sciences Information Services, Current Awareness in Biological Sci-ences, Current Contents®/Life Sciences, EMBASE/Excerpta Medica,Index Medicus, Medical Documentation Service®, PsycINFO, Refer-ence Update®, Research Alert®, Science Citation Index®, SciSearch®,and SIIC Data Bases. Copyright © 2008 by the American Society forPharmacology and Experimental Therapeutics. All rights reserved.Printed in the U.S.A.

Inhibition of Ca2�-Independent Phospholipase A2 DecreasesProstate Cancer Cell Growth by p53-Dependent andIndependent Mechanisms

Bin Sun, Xiaoling Zhang, Sonia Talathi, andBrian S. Cummings

59

Simvastatin Inhibits Staphylococcus aureus Host Cell Invasionthrough Modulation of Isoprenoid Intermediates

Mary P. Horn, Sharmon M. Knecht,Frances L. Rushing, Julie Birdsong,C. Parker Siddall, Charron M. Johnson,Terri N. Abraham, Amy Brown,Catherine B. Volk, Kelly Gammon,Derron L. Bishop, John L. McKillip, andSusan A. McDowell

135

Signal Transduction and Transcriptional Control of CardiacConnexin43 Up-Regulation after �1-Adrenoceptor Stimulation

Aida Salameh, Silke Krautblatter,Sabine Bae�ler, Sebastian Karl,Diana Rojas Gomez, Stefan Dhein, andDietrich Pfeiffer

315

CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPYA New O6-Alkylguanine-DNA Alkyltransferase InhibitorAssociated with a Nitrosourea (Cystemustine) Validates aStrategy of Melanoma-Targeted Therapy in Murine B16 andHuman-Resistant M4Beu Melanoma Xenograft Models

Maryse Rapp, Jean C. Maurizis,Janine Papon, Pierre Labarre, Ting-Di Wu,Alain Croisy, Jean L. Guerquin-Kern,Jean C. Madelmont, andEmmanuelle Mounetou

171

ENDOCRINE AND DIABETESAge-Dependent Development of Metabolic Derangement andEffects of Intervention with Pioglitazone in Zucker DiabeticFatty Rats

Zsuzsanna Szocs, Barbara Brunmair,Karin Stadlbauer, Peter Nowotny,Leonhardt Bauer, Anton Luger, andClemens Furnsinn

323

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENALEpidermal Growth Factor-Induced Esophageal Cancer CellProliferation Requires Transactivation of �-Adrenoceptors

Xuan Liu, William K. K. Wu, Le Yu,Zhi J. Li, Joseph J. Y. Sung, Shu T. Zhang,and Chi H. Cho

69

Therapeutic Potential of 1-Methylnicotinamide against AcuteGastric Lesions Induced by Stress: Role of EndogenousProstacyclin and Sensory Nerves

Tomasz Brzozowski, Peter C. Konturek,Stefan Chlopicki, Zbigniew Sliwowski,Michal Pawlik, Agata Ptak-Belowska,Slawomir Kwiecien, Danuta Drozdowicz,Robert Pajdo, Ewa Slonimska,Stanislaw J. Konturek, andWieslaw W. Pawlik

105

The Effect of Subchronic Administration of 7-(4-Fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methylcyclopropyl]methyl}-1H-pyrrolo[2,3-d]pyridazine(CS-526), a Novel Acid Pump Antagonist, on Gastric AcidSecretion and Gastrin Levels in Rats

Keiichi Ito, Kazuya Kinoshita,Atsuyuki Tomizawa,Yuka Morikawa-Inomata, Fumi Inaba,Yoshifumi Fujita, Keiichi Tabata, andNobuhiko Shibakawa

163

Effects of the �3-Adrenergic Receptor Agonist Disodium5-[(2R)-2-[[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316243) on Bladder Micturition Reflex inSpontaneously Hypertensive Rats

Lisa A. Leon, Bryan E. Hoffman,Scott D. Gardner, Nicholas J. Laping,Christopher Evans, Erin S. R. Lashinger, andXin Su

178

Hyperosmolarity-Induced Dilation and Epithelial BioelectricResponses of Guinea Pig Trachea in Vitro: Role of KinaseSignaling

Yi Jing, Janet A. Dowdy,Michael R. Van Scott, and Jeffrey S. Fedan

186

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA□S Effects of the cFMS Kinase Inhibitor 5-(3-Methoxy-4-((4-

methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580)in Normal and Arthritic Rats

James G. Conway, Heather Pink,Mandy L. Bergquist, Bajin Han,Scott Depee, Sarva Tadepalli, Peiyuan Lin,R. Christian Crumrine, Jane Binz,Richard L. Clark, Jeffrey L. Selph,Stephen A. Stimpson, Jeff T. Hutchins,Stanley D. Chamberlain, andThomas A. Brodie

41

Estrogen Receptor �: Expression Profile and PossibleAnti-Inflammatory Role in Disease

Matthew C. Catley, Mark A. Birrell,Elizabeth L. Hardaker, Jorge de Alba,Stuart Farrow, Saleem Haj-Yahia, andMaria G. Belvisi

83

The Function of the Human Interferon-�1a GlycanDetermined in Vivo

Lasse Dissing-Olesen,Morten Thaysen-Andersen,Michael Meldgaard, Peter Højrup, andBente Finsen

338

Insulin Activation of the Phosphatidylinositol 3-Kinase/ProteinKinase B (Akt) Pathway Reduces Lipopolysaccharide-InducedInflammation in Mice

Linda B. Kidd, Gernot A. Schabbauer,James P. Luyendyk, Todd D. Holscher,Rachel E. Tilley, Michael Tencati, andNigel Mackman

348

METABOLISM, TRANSPORT, AND PHARMACOGENOMICSEffect of Cysteine Mutagenesis on the Function and DisulfideBond Formation of Human ABCG2

Yang Liu, Youyun Yang, Jing Qi, Hui Peng,and Jian-Ting Zhang

33

A Catenary Model to Study Transport and Conjugation ofBaicalein, a Bioactive Flavonoid, in the Caco-2 CellMonolayer: Demonstration of Substrate Inhibition

Huadong Sun, Li Zhang,Edwin Chiu Yuen Chow, Ge Lin,Zhong Zuo, and K. Sandy Pang

117

□S Impact of Impurity on Kinetic Estimates from Transport andInhibition Studies

Pablo Gonzalez and James E. Polli 296

NEUROPHARMACOLOGYEffects of Palmitoylethanolamide on Signaling PathwaysImplicated in the Development of Spinal Cord Injury

Tiziana Genovese, Emanuela Esposito,Emanuela Mazzon, Rosanna Di Paola,Rosaria Meli, Placido Bramanti,Daniele Piomelli, Antonio Calignano, andSalvatore Cuzzocrea

12

Nicotinic Acetylcholine Receptors in the Anterior, but NotPosterior, Ventral Tegmental Area Mediate Ethanol-InducedElevation of Accumbal Dopamine Levels

Mia Ericson, Elin Lof, Rosita Stomberg,PeiPei Chau, and Bo Soderpalm

76

□S Differential Block of Sensory Neuronal Voltage-Gated SodiumChannels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine

Patrick L. Sheets, Cara Heers,Thomas Stoehr, and Theodore R. Cummins

89

Spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101) Treatment Rescues Olfactory Bulbectomy-InducedMemory Impairment by Activating Ca2�/Calmodulin KinaseII and Protein Kinase C in Mouse Hippocampus

Feng Han, Norifumi Shioda,Shigeki Moriguchi, Yui Yamamoto,Alisa Y. Ali Raie, Yoshimasa Yamaguchi,Masataka Hino, and Kohji Fukunaga

127

Transglutaminase-Catalyzed Transamidation: A NovelMechanism for Rac1 Activation by 5-Hydroxytryptamine2A

Receptor Stimulation

Y. Dai, N. L. Dudek, T. B. Patel, andN. A. Muma

153

Curcumin Structure-Function, Bioavailability, and Efficacy inModels of Neuroinflammation and Alzheimer’s Disease

Aynun N. Begum, Mychica R. Jones,Giselle P. Lim, Takashi Morihara,Peter Kim, Dennis D. Heath,Cheryl L. Rock, Mila A. Pruitt,Fusheng Yang, Beverly Hudspeth,Shuxin Hu, Kym F. Faull, Bruce Teter,Greg M. Cole, and Sally A. Frautschy

196

Evidence for the Role of Metabotropic Glutamate (mGlu)2Not mGlu3 Receptors in the Preclinical AntipsychoticPharmacology of the mGlu2/3 Receptor Agonist (�)-(1R,4S,5S,6S)-4-Amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic Acid (LY404039)

Matthew J. Fell, Kjell A. Svensson,Bryan G. Johnson, and Darryle D. Schoepp

209

Antihyperalgesic Effects of (R,E)-N-(2-Hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a Novel Transient Receptor PotentialVanilloid Type 1 Modulator That Does Not CauseHyperthermia in Rats

Sonya G. Lehto, Rami Tamir, Hong Deng,Lana Klionsky, Rongzhen Kuang, April Le,Doo Lee, Jean-Claude Louis, Ella Magal,Barton H. Manning, John Rubino,Sekhar Surapaneni, Nuria Tamayo,Tingrong Wang, Judy Wang, Jue Wang,Weiya Wang, Brad Youngblood,Maosheng Zhang, Dawn Zhu,Mark H. Norman, and Narender R. Gavva

218

□S Transposition of Three Amino Acids Transforms the HumanMetabotropic Glutamate Receptor (mGluR)-3-PositiveAllosteric Modulation Site to mGluR2, and AdditionalCharacterization of the mGluR2-Positive AllostericModulation Site

Blake A. Rowe, Herve Schaffhauser,Sylvia Morales, Laura S. Lubbers,Celine Bonnefous, Theodore M. Kamenecka,Jeffrey McQuiston, and Lorrie P. Daggett

240

n-Alcohols Inhibit Voltage-Gated Na� Channels Expressed inXenopus Oocytes

Takafumi Horishita and R. Adron Harris 270

Studies of the Biogenic Amine Transporters. 12. Identificationof Novel Partial Inhibitors of Amphetamine-InducedDopamine Release

Joseph J. Pariser, John S. Partilla,Christina M. Dersch,Subramaniam Ananthan, andRichard B. Rothman

286

Positive Modulation of GABAB Receptors Decreased NicotineSelf-Administration and Counteracted Nicotine-InducedEnhancement of Brain Reward Function in Rats

Neil E. Paterson, Styliani Vlachou,Sebastien Guery, Klemens Kaupmann,Wolfgang Froestl, and Athina Markou

306

TOXICOLOGYp38 Mitogen-Activated Protein Kinase-Dependent TumorNecrosis Factor-�-Converting Enzyme Is Important for LiverInjury in Hepatotoxic Interaction between Lipopolysaccharideand Ranitidine

Xiaomin Deng, Jingtao Lu,Lois D. Lehman-McKeeman, Ernst Malle,David L. Crandall, Patricia E. Ganey, andRobert A. Roth

144

Deferiprone Does Not Protect against Chronic AnthracyclineCardiotoxicity in Vivo

Olga Popelova, Martin Sterba,Tomas Simunek, Yvona Mazurova,Ivana Guncova, Milos Hroch,Michaela Adamcova, and Vladimır Gersl

259

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

About the cover: Loss of mitochondrial membrane potential in NF90-8 cells following FTI/lovastatincombination treatment. See the article by Wojtkowiak et al. on page 1 of this issue.