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The Journal of PHARMACOLOGY And Experimental Therapeutics A Publication of the American Society for Pharmacology and Experimental Therapeutics May 2004 Vol. 309, No. 2 Contents PERSPECTIVES IN PHARMACOLOGY Academic Pharmacologists: Confronting New Challenges in Edward D. French Educational Programs of Graduate and Health Care Professionals 469 720 ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION Brain Uptake of the Glucagon-Like Peptide-1 Antagonist 730 Exendin(9-39) after Intranasal Administration William A. Banks, Matthew J. During, and Age-Related Differences in CYP3A Expression and Activity in the Michael L. Niehoff Rat Liver, Intestine, and Kidney Jill S. Warrington, David J. Greenblatt, and The Effect of Age on P-Glycoprotein Expression and Function in Lisa L. von Moltke the Fischer-344 Rat Jill S. Warrington, David J. Greenblatt, and Lisa L. von Moltke BEHAVIORAL PHARMACOLOGY 650 The Discriminative Stimulus Effects of -y-Hydroxybutyrate and Related Compounds in Rats Discriminating Baclofen or Diazepam: L. P. Carter, A. W. Unzeitig, H. Wu, The Role of GABAB and GABAA Receptors W. Chen, A. Coop, W. Koek, and C. P. France Effects of iV-Substituted Analogs of Benztropine: Diminished Cocaine-Like Effects in Dopamine Transporter Ligands Jonathan L. Kalz, Theresa A. Kopajtic. Gregory E. Agoston, and Amy Hauck CARDIOVASCULAR Newman 490 An Antiarrhythmic Effect of a Chymase Inhibitor after Myocardial Infarction Denan Jin, Shinji Takai, Masato Sakaguchi, Yukiko Okamoto, Michiko Muramatsu, and Mizuo Pharmacological Characterization of N-tert-ftutyl~N'-[2-(<l'Miyazaki methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Jean-Michel Dogne, Julien Hanson, Xavier de Leval, 498 Novel Thromboxane A2 Receptor Antagonist and Philippe Kolh, Vincent Tchana-Sato, Thromboxane Synthase Inhibitor in a Rat Model of Arterial Laurence de Leva!, Stephanie Rolin, Thrombosis and Its Effects on Bleeding Time Alexandre Ghuysen, Patrick Segers, Bernard Lambermont, Bernard Masereel, and Bernard Pirotte Risk of Ventricular Proarrhythmia with Selective Opening of the Myocardial Sarcolemmal versus Mitochondrial ATP554 Peter S. Fischbach, Andrew White, Terrance D. Gated Potassium Channel Barrett, and Benedict R. Lucchesi Cardioprotection of Interleukin-2 Is Mediated via K-Opioid 560 Chun-Mei Cao, Qiang Xia, Jie Tu, Receptors Mai Chen, Song Wu, and Tak-Ming Wong Atypical p-Adrenoceptor Subtypes Mediate Relaxations of Rabbit Corpus Cavernosum Cleber E. Teixeira, Juliana S. Baracat, 587 Angelina Zanesco,Adson Antunes and Gilberto De Nucci Kokichi Suzuki, Yuko Muto, Kenichi Fushihara, Ken-ichi Kanemoto, Hiroyuki Iida, Eriko Sato, Chika Kikuchi, Tetsuya Matsushima, Emiko Kato, Masahiro Nomoto, Shin Yoshioka, and Hidemi Ishii Kenji Okajima, Naoaki Harada, Mitsuhiro Uchiba, and Hirotaka Isobe 607 Specific Endothetin ETA Receptor Antagonism Does Not Modulate Insulin-Induced Hemodynamic Effects in the Human Kidney, Eye, or Forearm Anna Rab, Susanne Dallinger, Kaija Polak, Johannes Pleiner, Elzbieta Polska, Michael Wolzt, and Leopold Schmetterer 692 Immune Cell Regulation and Cardiovascular Effects of Sphingosine 1-Phosphate Receptor Agonists in Rodents Are Mediated via Distinct Receptor Subtypes M. Forrest, S.-Y. Sun, R. Hajdu, J. Bergstrom, D. Card, G. Doherty, J. Hale, C. Keohane, C. Meyers, J. Milligan, S. Mills, N. Nomura, H. Rosen, M. Rosenbach, G.-J. Shei, I. I. Singer, M. Tian, S. West, V. While, J. Xie, R. L. Proia, and S. Mandala 758 Histamine H, and H2 Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans Naoyuki Matsuda, Subrina Jesmin, Yoshika Takahashi, Eiicbiro Hatta, Masanobu Kobayashi, Kazuto Matsuyama, Nozomi Kawakami, Ichiro Sakuma, Satoshi Gando, Hiyoyuki Fukui, Yuichi Hattori, and Roberto Levi 786 5-Hydroxytryptamine,n Receptor-Mediated Contraction of Rabbit Saphenous Vein and Basilar Artery: Role of Vascular Endothelium The Fenfluramine Metabolite (+)-Norfenfluramine Is Vasoactive Anindya Bhattacharya, Kathryn W. Schenck, Yao-Chang Xu, Laura Nisenbaum, Elizabeth Galbreath, and Marlene L. Cohen Wei Ni, Melissa W. Li, Keshari Thakali, Gregory D. Fink, and Stephanie W. Watts 825 Enhancement of Fibrinolysis by EF626S ((S)-7-Amino-2-[[[(«)2-methyl-l-(3-phenylpropanoylamino)propyl] hydroxyphosphinoyl]methyl]heptanoic Acid), a Specific Inhibitor of Plasma Carboxypeptidase B Activation of Capsaicin-Sensitive Sensory Neurons by Carvedilol, a Nonselective 6-Blocker, in Spontaneous Hypertensive Rats CELLULAR AND MOLECULAR Evidence for Multiple P2Y Receptors in T rabecular Meshwork Cells Pharmacological and Signaling Properties of Endogenous P2Y1 Receptors in Cystic Fibrosis Transmembrane Conductance Regulator-Expressing Chinese Hamster Ovary Cells Oxidation of Protein Tyrosine Phosphatases as a Pharmaceutical Mechanism of Action: A Study Using 4Hydroxy-3,3-dimethyl-2//-benzoIg]indole-2,5(3i/>Dione Prostaglandin Ethanolamides (Prostamides): In Vitro Pharmacology and Metabolism 684 845 Craig E. Crosson, Phillip W. Yates, Aruna N. Bhat, Yurii V. Mukhin, and Shahid Husain Brice Marcet, ValSrie Chappe, Patrick Delmas, and Bernard Verrier 484 Charlotta Liljebris, Pawel Baranczewski, Eva Bjorkstrand, Styrbjorn Bystrom, Bo Lundgren, Agneta Tjernberg, Malin Warolen, and Stephen R. James 711 I. Matias, J. Chen, L. De Petrocellis, T. Bisogno, A. Ligresti, F. Fezza, A.H.-P. Krauss, L. Shi, C. E. Protzman, C. Li, Y. Liang, A. L. Nieves, K. M. Kedzie, R. M. Burk, V. Di Marzo, and D. F. Woodward 745 Daniela A. Eisinger and RUdiger Schulz 776 Charlene R. Johnson, Jiong Chun, Robert Bittman, and W. David Jarvis 452 Qiwei Zhang, David W. Ohannesian, and Leonard C. Erickson 506 Amanda P. Struckhoff, Robert Bittman, Matthew E. Burow, Sanda Clejan, Steven Elliott, Timothy Hammond, Yan Tang, and Barbara S. Beckman 523 Edward A. Neuwelt, Michael A. Pagel, Dale F. Kraemer, Darryl R. Peterson, and Leslie L. Muldoon 594 533 Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinases Block Internalization of 5-Opioid Receptors CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY Intrinsic Cytotosicity and Chcmomodulatory Actions of Novel Phenethylisothiocyanate Sphingoid Base Derivatives in HL-60 Human Promyelocytic Leukemia Cells Hammerhead Ribozyme-Mediated Sensitization of Human Tumor Cells after Treatment with l,3-Bis(2-chloroethyl)-lnitrosourea Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer Bone Marrow Chemoprotection without Compromise of Chemotherapy Efficacy in a Rat Brain Tumor Model ENDOCRINE AND REPRODUCTIVE Robert N. Pechnick and Russell E. Poland 515 David E. Potter, Karen R. M. Russell, and Marlina Manhiani 548 Shuhei Tomimoto, Hitoshi Hashimoto, Norihito Shintani, Kyohei Yamamoto, Yuki Kawabata, Ken-Ichi Hamagami, Kazuya Yamagata, Jun-Ichiro Miyagawa, and Akemichi Baba 796 Niel C. Hoglen, Long-Shiuh Chen, Craig D. Fisher, Brad P. Hirakawa, Todd Groessl, and Patricia C. Contreras 634 Tumor Necrosis Factor-a-Induced Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production by Rat Gastric Epithelial Cells: Role of Reactive Oxygen Species and Nuclear Factories Osamu Handa, Yiiji Naito, Tomohisa Takagi, Makoto Shimozawa, Satoshi Kokura, Norimasa Yoshida, Hirofumi Matsui, Gediminas Cepinskas, Peter R. Kvietys, and Toshikazu Yoshikawa 670 Role of Adenosine A2A Receptor in the Regulation of Gastric Somatostatin Release Linda Yip and Yin Nam Kwok 804 Genya Gekker, Shuxian Hu, Mark P. Wentland, Jean M. Bidlack, James R. Lokensgard, and Phillip K. Peterson 600 John L. Wallace, Marcelo N. Muscarl, Gilberto de Nucci, Stella Zamuner, Giuseppe Cirino, Piero del Soldato, and Ennio Ongini 626 Jean Gougat, Bernard Ferrari, Lionel Sarran, Claudine Planchenault, Martine Poncelet, Jeanne Maruani, Richard Alonso, Annie Cudennec, Tiziano Croci, Fabio Guagnini, Katalin Urban-Szabo, Jean-Pierre MartinoIIe, Philippe Soubrie, Olivier Finance, and Gerard Le Fur 661 Cuifen Hou, Thomas Kirchner, Monica Singer, Michele Matheis, Dennis Argentieri, and Druie Cavender 697 Chang Seok Park, Hyun Lim, Kee Jung Han, Sun Heum Baek, Hyung Ok Sohn, Dong Wook Lee, Yang-Gyun Kim, Hye-Young Yun, Kwang Jin Baek, and Nyoun Soo Kwon 705 Koremu K. Meja, Matthew C. Catley, Lisa M. Cambridge, Peter J. Barnes, Hazel Lum, Robert Newton, and Mark A. Giembycz 833 Kar-Chan Choong and Roh-Yu Shen 444 Francesco Crespi and Zvani L. Rossetti 462 Thomas F. Finnegan, De-Pei Li, Shao-Rui Chen, and Hui-Lin Pan 476 Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-PituitaryAdrenal Axis Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility Overexpression of Pituitary Adenylate Cyclase-Activating Polypeptide in Islets Inhibits Hyperinsulinemia and Islet Hyperplasia in Agouti Yellow Mice GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL Characterization of IDN-6556 (3-{2-[2-tert-Butylphenylaminooxalyl)-amino]-propionylamino}-4-oxo-5-(2,3,5,6tetrafluoro-phenoxy)-pentanoic Acid): a Liver-Targeted Caspase Inhibitor -^ INFLAMMATION AND IMMUNOPHARMACOLOGY K-Opioid Receptor Ligands Inhibit Cocaine-Induced HIV-1 Expression in Microglial Cells Gastric Tolerability and Prolonged Prostaglandin Inhibition in the Brain with a Nitric Oxide-Releasing Flurbiprofen Derivative, NCX-2216 [3-[4-(2-Fluoro-a-methyl-[l,lbiphenyI]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4nitrooxy butyl ester] SSR240612IX2tf)-2-[((3/0-3-(l,3-BenzodioxoI-5-yl)-3-{[(6methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4{|2tf,6S)-2,6-dimethylpiperidinyl]methyI}phenyl)-iV-isopropyliV-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B t Receptor: Biochemical and Pharmacological Characterization In Vivo Activity of a Phospholipase C Inhibitor, l-(6-((17/3-3Mcthoxyestra-1,3,5( 10)-trien- 17-yl)amino)hexyl)- l#-py rrole2,5-dione (U73122), in Acute and Chronic Inflammatory Reactions Inhibition of Nitric Oxide Generation by 23,24Dihydrocucurbitacin D in Mouse Peritoneal Macrophages Adenovirus-Mediated Delivery and Expression of a cAMPDependent Protein Kinase Inhibitor Gene to BEAS-2B Epithelial Cells Abolishes the Anti-Inflammatory Effects of Rolipram, Salbutamol, and Prostaglandin E 2: A Comparison with H-89 NEUROPHARMACOLOGY Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission Pulse of Nitric Oxide Release in Response to Activation of NMethyl-D-aspartate Receptors in the Rat Striatum: Rapid Desensitization, Inhibition by Receptor Antagonists, and Potentiation by Glycine Activation of /*-Opioid Receptors Inhibits Synaptic Inputs to Spinally Projecting Rostral Ventromedial Medulla Neurons A Novel Selective Allosteric Modulator Potentiates the Activity of Native Metabotropic Glutamate Receptor Subtype 5 in Rat Forebrain Julie A. O'Brien, Wei Lemaire, Marion Wittmann, Marlene A. Jacobson, Sookhee N. Ha, David D. Wisnoski, Craig W. Lindsley, Herve J. Schaffhauser, Blake Rowe, Cyrille Sur, Mark E. Duggan, Douglas J. Pettibone, P. Jeffrey Conn, and David L. Williams, Jr. 568 Alterations in Vesicular Dopamine Uptake Contribute to Tolerance to the Neurotoxic Effects of Methamphetamine Kamisha L. Johnson-Davis, Jannine G. Truong, Annette E. Fleckenstein, and Diana G. Wilkins 578 Protein Kinase C e and y: Involvement in Formalin-Induced Nociception in Neonatal Rats Sarah M. Sweitzer, Shirley M. E. Wong, Michael C. Peters, Daria Mochly-Rosen, David C. Yeomans, and Joan J. Kendig 616 Phytoestrogen Cimicifugoside-Mediated Inhibition of Catecholamine Secretion by Blocking Nicotinic Acetylcholine Receptor in Bovine Adrenal Chroniaffin Cells Kyung-Chul Woo, Yong-Soo Park, Dong-Jae Jun, Jeong-Ok Lim, Woon-Yi Baek, Byung-Sun Suh, and Kyong-Tai Kim 641 Enantioselectivity of o:-Benzy la-methyl-y-butyrolactoneMediated Modulation of Anticonvulsant Activity and GABAA Receptor Function Eric B. Gonzales, Cathy L. Bell-Horner, Maria Antonette M. de la Cruz, James A. Ferrendelli, Douglas F. Covey, and Glenn H. Dillon 677 Dopaminergic Agonists and Muscarinic Antagonists Improve Lateralization in Hemiparkinsonian Rats in a Novel Exploratory Y-Maze Makoto Nakagawa, Makoto Ohgoh, Yukio Nishizawa, and Hiroo Ogura 737 Fast Onset Medications through Thermally Generated Aerosols Joshua D. Rabinowitz, Martin Wensley, Peter Lloyd, Daniel Myers, William Shen, Amy Lu, Craig Hodges, Ron Hale, Daniel Mufson, and Alejandro Zaffaroni 769 Differential Conditioned Place Preference Responses to Endomorphin-1 and Endomorphin-2 Microinjected into the Posterior Nucleus Accumbens Shell and Ventral Tegmental Area in the Rat Maia Terashvili, Hsiang-en Wu, Randy J. Leitermann, Kuei-chun Hung, Andrew D. Clithero, Emma T. Schwasinger, and Leon F. Tseng 816