The Journal of PHARMACOLOGY

And Experimental Therapeutics

A Publication of the American Society for Pharmacology and Experimental Therapeutics

January 2006 Vol. 316, No. 1 Contents

PERSPECTIVES IN PHARMACOLOGY The Role of Protein Kinase C Isoforms in Modulating Injury A. Farhadi, A. Keshavarzian, Z. Ranjbaran, 1 and Repair of the Intestinal Barrier J. Z. Fields, and A. Banan ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION Downloaded from Evaluation of Tributyrin Lipid Emulsion with Affinity to Low- Jie Su, Li He, Ningning Zhang, and 62 Density Lipoprotein: Pharmacokinetics in Adult Male Wistar Paul C. Ho Rats and Cellular Activity on Caco-2 and HepG2 Cell Lines Sexually Dimorphic Regulation of Hepatic Isoforms of Human Ravindra N. Dhir, Wojciech Dworakowski, 87 Cytochrome P450 by Growth Hormone Chellappagounder Thangavel, and Bernard H. Shapiro jpet.aspetjournals.org The Dual Actions of Morin (3,5,7,2,4-Pentahydroxyflavone) Zhifeng Yu, Wing Ping Fong, and 169 as a Hypouricemic Agent: Uricosuric Effect and Xanthine Christopher H. K. Cheng Oxidase Inhibitory Activity Preparation of a Claudin-Targeting Molecule Using a C- Chiaki Ebihara, Masuo Kondoh, 255 Terminal Fragment of Clostridium perfringens Enterotoxin Naoki Hasuike, Motoki Harada, Hiroyuki Mizuguchi, Yasuhiko Horiguchi, Makiko Fujii, and Yoshiteru Watanabe at ASPET Journals on September 26, 2021 Inactivation of CYP2A6 and CYP2A13 during Nicotine Linda B. von Weymarn, Kathryn M. Brown, 295 Metabolism and Sharon E. Murphy

□S The Utility of in Vitro Cytochrome P450 Inhibition Data in R. Scott Obach, Robert L. Walsky, 336 the Prediction of Drug-Drug Interactions Karthik Venkatakrishnan, Emily A. Gaman, J. Brian Houston, and Larry M. Tremaine The Impact of Plasma Protein Binding on the Renal Daniel A. J. Bow, Jennifer L. Perry, 349 Transport of Organic Anions John D. Simon, and John B. Pritchard A Biosynthetic Pathway Generating 12-Hydroxy-5,8,14- Liping Du, Valery Yermalitsky, 371 eicosatrienoic Acid from Arachidonic Acid Is Active in Mouse David L. Hachey, Setti G. Jagadeesh, Skin Microsomes John R. Falck, and Diane S. Keeney BEHAVIORAL PHARMACOLOGY Depressive-Like Effects of the ␬-Opioid Receptor Agonist William A. Carlezon, Jr., Ce´cile Be´guin, 440 Salvinorin A on Behavior and Neurochemistry in Rats Jennifer A. DiNieri, Michael H. Baumann, Michele R. Richards, Mark S. Todtenkopf, Richard B. Rothman, Zhongze Ma, David Y.-W. Lee, and Bruce M. Cohen CARDIOVASCULAR YC-1 [3-(5-Hydroxymethyl-2-furyl)-1-benzyl Indazole] Yi-Nan Liu, Shiow-Lin Pan, Chieh-Yu Peng, 35 Inhibits Neointima Formation in Balloon-Injured Rat Carotid Jih-Hwa Guh, Dong-Ming Huang, through Suppression of Expressions and Activities of Matrix Ya-Ling Chang, Chun-Hung Lin, Metalloproteinases 2 and 9 Hui-Chen Pai, Sheng-Chu Kuo, Fang-Yu Lee, and Che-Ming Teng

The Journal of Pharmacology and Experimental Therapeutics (ISSN Single copy: $82.00. 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.: $817.00 Index®, SciSearch®, and SIIC Data Bases. Copyright © 2006 by the for institutions and $356.00 for non-ASPET members. Outside the American Society for Pharmacology and Experimental Therapeutics. U.S.: $964.00 for institutions and $502.00 for non-ASPET members. All rights reserved. Printed in the U.S.A. Increased Superoxide Anion Production by Interleukin-1␤ Francesc Jime´nez-Altayo´, Ana M. Briones, 42 Impairs Nitric Oxide-Mediated Relaxation in Resistance Jesu´s Giraldo, Anna M. Planas, Arteries Mercedes Salaices, and Elisabet Vila Pressor Responses to Ephedrine Are Mediated by a Direct John T. Liles, Paul A. Dabisch, 95 Mechanism in the Rat Keith E. Hude, Leena Pradhan, Kurt J. Varner, Johnny R. Porter, Alissa R. Hicks, Conni Corll, Syed R. Baber, and Philip J. Kadowitz Hyperlipidemia Attenuates the Infarct Size-Limiting Effect of Zolta´n Giricz, Manoj M. Lalu, 154 Ischemic Preconditioning: Role of Matrix Metalloproteinase-2 Csaba Csonka, Pe´ter Bencsik, Inhibition Richard Schulz, and Pe´ter Ferdinandy The Amiodarone Derivative KB130015 [2-Methyl-3-(3,5- Virginie Bito, Dieter Dauwe, 162 diiodo-4-carboxymethoxybenzyl)benzofuran] Induces an Na؉- Fons Verdonck, Kanigula Mubagwa, and Dependent Increase of [Ca2؉] in Ventricular Myocytes Karin R. Sipido Dosing Time-Dependent Effect of Temocapril on the Mortality Masahiko Nozawa, Koh-ichi Sugimoto, 176 of Stroke-Prone Spontaneously Hypertensive Rats Masami Ohmori, Hitoshi Ando, and Akio Fujimura

Bepridil, an Antiarrhythmic Drug, Opens Mitochondrial KATP Toshiaki Sato, Alexandre D. T. Costa, 182 Channels, Blocks Sarcolemmal KATP Channels, and Confers Tomoaki Saito, Takehiko Ogura, Cardioprotection Hideyuki Ishida, Keith D. Garlid, and Downloaded from Haruaki Nakaya Blockade of Electron Transport before Cardiac Ischemia with Qun Chen, Charles L. Hoppel, and 200 the Reversible Inhibitor Amobarbital Protects Rat Heart Edward J. Lesnefsky Mitochondria Chronic Ethanol Consumption Enhances Phenylephrine- Carlos R. Tirapelli, Johny Al-Khoury, 233 Induced Contraction in the Isolated Rat Aorta Ghassan Bkaily, Pedro D’Orle´ans-Juste, jpet.aspetjournals.org Vera L. Lanchote, Sergio A. Uyemura, and Ana M. de Oliveira A Nonthiazolidinedione Peroxisome Proliferator-Activated Andrew G. Howarth, William B. Wiehler, 364 Receptor ␥ Agonist Reverses Endothelial Dysfunction in Malarvannan Pannirselvam, Yanfen Jiang, ,Diabetic (db/db؊/؊) Mice Joel P. Berger, David Severson Todd J. Anderson, and Chris R. Triggle Multiple Cellular Electrophysiological Effects of a Novel Gwo-Jyh Chang, Ming-Jai Su, 380 at ASPET Journals on September 26, 2021 Antiarrhythmic Furoquinoline Derivative HA-7 [N-Benzyl-7- Sheng-Chu Kuo, Tsung-Ping Lin, and methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione] in Ying-Shiung Lee Guinea Pig Cardiac Preparations ␤ Induction of 3-Adrenergic Receptor Functional Expression Rene´e Germack and John M. Dickenson 392 following Chronic Stimulation with Noradrenaline in Neonatal Rat Cardiomyocytes ARD-353 [4-((2R,5S)-4-(R)-(4-Diethylcarbamoylphenyl)(3- Michael. J. Watson, Jonathon D. S. Holt, 423 hydroxyphenyl)methyl)-2,5-dimethylpiperazin-1-ylmethyl)- Scott J. O’Neill, Ke Wei, benzoic Acid], A Novel Nonpeptide ␦ Receptor Agonist, William Pendergast, Garrett J. Gross, Reduces Myocardial Infarct Size without Central Effects Peter J. Gengo, and Kwen-Jen Chang

CELLULAR AND MOLECULAR Nitric Oxide-Donating Aspirin Inhibits Colon Cancer Cell Thomas R. Hundley and Basil Rigas 25 Growth via Mitogen-Activated Protein Kinase Activation HIV Protease Inhibitors: Suppression of Insulin Secretion by Yvonne Neye, Martina Du¨fer, Gisela Drews, 106 Inhibition of Voltage-Dependent K؉ Currents and Anion and Peter Krippeit-Drews Currents Molecular Mechanisms for Large Conductance Ca2؉- Kazuho Sakamoto, Taro Nonomura, 144 ,Activated K؉ Channel Activation by a Novel Opener, 12,14- Susumu Ohya, Katsuhiko Muraki Dichlorodehydroabietic Acid Tomohiko Ohwada, and Yuji Imaizumi 3-O-Acetyl-11-keto-boswellic Acid Decreases Basal Daniel Poeckel, Lars Tausch, Sven George, 224 Intracellular Ca2؉ Levels and Inhibits Agonist-Induced Ca2؉ Johann Jauch, and Oliver Werz Mobilization and Mitogen-Activated Protein Kinase Activation in Human Monocytic Cells

□S Niemann-Pick C1 Protein Facilitates the Efflux of the Yuping Gong, Muralikrishna Duvvuri, 242 Anticancer Drug Daunorubicin from Cells According to a Michael B. Duncan, Jian Liu, and Novel Vesicle-Mediated Pathway Jeffrey P. Krise

Constitutive Activity and Inverse Agonism at the M2 Carl P. Nelson, Stefan R. Nahorski, and 279 Muscarinic Acetylcholine Receptor R. A. John Challiss Proline 326 in the C Terminus of Murine CX3CR1 Prevents Christopher N. Davis and 356 G-Protein and Phosphatidylinositol 3-Kinase-Dependent Jeffrey K. Harrison Stimulation of Akt and Extracellular Signal-Regulated Kinase in Chinese Hamster Ovary Cells Erythropoietin Receptor Signal Transduction Requires Sumaya N. Hamadmad, Matthew K. Henry, 403 Protein Geranylgeranylation and Raymond J. Hohl The Mitogen-Activated Protein Kinase/Extracellular Signal- Raymond R. Mattingly, Janice M. Kraniak, 456 Regulated Kinase Kinase Inhibitor PD184352 (CI-1040) Joshua T. Dilworth, Patricia Mathieu, Selectively Induces Apoptosis in Malignant Schwannoma Cell Beverly Bealmear, James E. Nowak, Lines Joyce A. Benjamins, Michael A. Tainsky, and John J. Reiners, Jr.

CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY Hpr6 (Heme-1 Domain Protein) Regulates the Susceptibility of Gerard Crudden, Rachel E. Chitti, and 448 Cancer Cells to Chemotherapeutic Drugs Rolf J. Craven

ENDOCRINE AND DIABETES Long-Term Treatment with Novel Glycogen Synthase Kinase- Oksana Kaidanovich-Beilin and 17 3 Inhibitor Improves Glucose Homeostasis in ob/ob Mice: Hagit Eldar-Finkelman Molecular Characterization in Liver and Muscle

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL Expression and Response to Angiotensin-Converting Enzyme Juliane Bolbrinker, Snezana Markovic, 8 Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Markus Wehland, Glomerular Damage in Young Transgenic Rats with Renin- Wynand B. W. H. Melenhorst, Downloaded from Dependent Hypertension Harry van Goor, and Reinhold Kreutz Evidence That Hydrogen Sulfide Exerts Antinociceptive Eleonora Distrutti, Luca Sediari, 325

Effects in the Gastrointestinal Tract by Activating KATP Andrea Mencarelli, Barbara Renga, Channels Stefano Orlandi, Elisabetta Antonelli, Fiorenza Roviezzo, Antonio Morelli, Giuseppe Cirino, John L. Wallace, and Stefano Fiorucci jpet.aspetjournals.org Energy Homeostasis and Gastric Emptying in Ghrelin B. De Smet, I. Depoortere, D. Moechars, 431 Knockout Mice Q. Swennen, B. Moreaux, K. Cryns, J. Tack, J. Buyse, B. Coulie, and T. L. Peeters

INFLAMMATION AND IMMUNOPHARMACOLOGY

Activation of the Adenosine A3 Receptor in RAW 264.7 Cells Lynn Martin, Sandeep C. Pingle, 71

Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Daniel M. Hallam, Leonard P. Rybak, and at ASPET Journals on September 26, 2021 Factor-␣ Release by Reducing Calcium-Dependent Activation Vickram Ramkumar of Nuclear Factor-␬B and Extracellular Signal-Regulated Kinase 1/2 Inhibition of Inducible Nitric-Oxide Synthase Expression by Ru Zhou, Shen-Xi Zheng, Wei Tang, 121 (5R)-5-hydroxytriptolide in Interferon-␥- and Bacterial Pei-Lan He, Xiao-Yu Li, Yi-Fu Yang, Lipopolysaccharide Stimulated Macrophages Yuan-Chao Li, Jian-Guo Geng, and Jian-Ping Zuo Antiexudative Effects of Opioids and Expression of ␬- and Natalia Jime´nez, Margarita M. Puig, and 261 ␦-Opioid Receptors during Intestinal Inflammation in Mice: Olga Pol Involvement of Nitric Oxide Blockade of Nuclear Factor-␬B Signaling Pathway and Anti- Jeong-Hyung Lee, Haeng Sun Jung, 271 Inflammatory Activity of Cardamomin, a Chalcone Analog Phan Minh Giang Xuejun Jin, Sangku Lee, from Alpinia conchigera Phan Tong Son, Dongho Lee, Young-Soo Hong, Kyeong Lee, and Jung Joon Lee

NEUROPHARMACOLOGY Evaluation of Drug Penetration into the Brain: A Double Ve´ronique Josserand, He´le`ne Pe´lerin, 79 Study by in Vivo Imaging with Positron Emission Be´atrice de Bruin, Benoıˆt Jego, Tomography and Using an in Vitro Model of the Human Bertrand Kuhnast, Franc¸oise Hinnen, Blood-Brain Barrier Fre´de´ric Duconge´, Raphae¨l Boisgard, Fre´de´ric Beuvon, Francine Chassoux, Catherine Daumas-Duport, Eric Ezan, Fre´de´ric Dolle´, Aloı¨se Mabondzo, and Bertrand Tavitian Dopamine-Mediated Disinhibition in the CA1 Region of Rat Hana Hammad and John J. Wagner 113

Hippocampus via D3 Receptor Activation Characterization of Prejunctional Serotonin Receptors Gianluigi D’Agostino, Anna M. Condino, 129 Modulating [3H]Acetylcholine Release in the Human Detrusor Paola Gallinari, Gian P. Franceschetti, and Marcello Tonini Targeted Antioxidative and Neuroprotective Properties of the R. Danzeisen, B. Schwalenstoecker, 189 Dopamine Agonist Pramipexole and Its Nondopaminergic F. Gillardon, E. Buerger, V. Krzykalla, ,Enantiomer SND919CL2x [(؉)2-Amino-4,5,6,7-tetrahydro-6-L- K. Klinder, L. Schild, B. Hengerer propylamino-benzathiazole Dihydrochloride] A. C. Ludolph, C. Dorner-Ciossek, and L. Kussmaul Volatile Anesthetic Effects on Glutamate versus GABA Robert I. Westphalen and 208 Release from Isolated Rat Cortical Nerve Terminals: Basal Hugh C. Hemmings, Jr. Release Volatile Anesthetic Effects on Glutamate versus GABA Robert I. Westphalen and 216 Release from Isolated Rat Cortical Nerve Terminals: 4- Hugh C. Hemmings, Jr. Aminopyridine-Evoked Release Tobacco Smoke Chemicals Attenuate Brain-to-Blood Jennifer R. Paulson, Karen E. Roder, 248 Potassium Transport Mediated by the Na,K,2Cl- Ghia McAfee, David D. Allen, Cotransporter during Hypoxia-Reoxygenation Cornelis J. Van der Schyf, and Thomas J. Abbruscato Ketamine Produces Lasting Disruptions in Encoding of Christina R. Maxwell, 315 Sensory Stimuli Richard S. Ehrlichman, Yuling Liang, Danielle Trief, Stephen J. Kanes, Jonathan Karp, and Steven J. Siegel TPA023 [7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3- John R. Atack, Keith A. Wafford, 410 Downloaded from ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], Spencer J. Tye, Susan M. Cook, ␣ ␣ an Agonist Selective for 2- and 3-Containing GABAA Bindi Sohal, Andrew Pike, Cyrille Sur, Receptors, Is a Nonsedating Anxiolytic in Rodents and David Melillo, Linda Bristow, Primates Fran Bromidge, Ian Ragan, Julie Kerby, Les Street, Robert Carling, Jose´L. Castro, Paul Whiting, Gerard R. Dawson, and

Ruth M. McKernan jpet.aspetjournals.org Systemic and Intrathecal Effects of a Novel Series of Tony L. Yaksh, George Kokotos, 466

Phospholipase A2 Inhibitors on Hyperalgesia and Spinal Camilla I. Svensson, Daren Stephens, Prostaglandin E2 Release Christoforos G. Kokotos, Bethany Fitzsimmons, Dimitra Hadjipavlou-Litina, Xiao-Ying Hua, and Edward A. Dennis

TOXICOLOGY at ASPET Journals on September 26, 2021 Neurotoxicity of Ecstasy Metabolites in Rat Cortical Neurons, Joa˜o Paulo Capela, Andreas Meisel, 53 and Influence of Hyperthermia Artur Reis Abreu, Paula Se´rio Branco, Luı´sa Maria Ferreira, Ana Maria Lobo, Fernando Remia˜o, Maria Lurdes Bastos, and Fe´lix Carvalho Deltamethrin, a Pyrethroid Insecticide, Is a Potent Inducer for Lisa Imamura, Makoto Yasuda, 136 the Activity-Dependent Gene Expression of Brain-Derived Kozue Kuramitsu, Daichi Hara, Neurotrophic Factor in Neurons Akiko Tabuchi, and Masaaki Tsuda 4,4-Methylenedianiline-Induced Hepatotoxicity Is Modified by Xiaoyan Zhang, Jason C. Lambert, 289 N-Acetyltransferase 2 (NAT2) Acetylator Polymorphism in the Mark A. Doll, Jason M. Walraven, Rat Gavin E. Arteel, and David W. Hein Arsenic Trioxide Induces Apoptosis of Human Monocytes Anthony Lemarie, Claudie Morzadec, 304 during Macrophagic Differentiation through Nuclear Factor- Delphine Me´rino, Olivier Micheau, ␬B-Related Survival Pathway Down-Regulation Olivier Fardel, and Laurent Vernhet

LETTERS TO THE EDITOR Comments on “Isobolographic Analysis for Combinations of a J. Ignacio Lorenzo and Paula Sa´nchez-Marı´n 476 Full and Partial Agonist: Curved Isoboles” Response to Comments on “Isobolographic Analysis for Ronald J. Tallarida 479 Combinations of a Full and Partial Agonist: Curved Isoboles”

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

About the cover: Whole-body PET images acquired over 2 min after the intravenous injection of the [18F]fluoropyridinyl derivatives. See the article by Josserand et al. on page 79 of this issue.