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The Journal of
PHARMACOLOGY
PERSPECTIVES IN PHARMACOLOGY
Preclinical Assessment of Candidate Analgesic Drugs: Recent
Advances and Future Challenges
BEHAVIORAL PHARMACOLOGY
Effect of Duration and Pattern of Chronic Ethanol Exposure
on Tolerance to the Discriminative Stimulus Effects of
Ethanol in C57BL/6J Mice
The Dopamine Agonist Piribedil with L-DOPA Improves
Attentional Dysfunction: Relevance for Parkinson’s Disease
CARDIOVASCULAR
Fibroblast Growth Factor-2 Mediates Angiotensin-Converting
Enzyme Inhibitor-Induced Angiogenesis in Coronary
Endothelium
S. S. Negus, T. W. Vanderah, M. R. Brandt,
E. J. Bilsky, L. Becerra, and D. Borsook
507
Howard C. Becker and Alicia M. Baros 871
Nathalie Turle-Lorenzo, Béatrice Maurin,
Carole Puma, Claire Chezaubernard,
Philippe Morain, Christelle Baunez,
André Nieoullon, and Marianne Amalric
Sandra Donnini, Raffaella Solito,
Antonio Giachetti, Harris J. Granger,
Marina Ziche, and Lucia Morbidelli
□S Soluble Guanylyl Cyclase Activation Promotes Angiogenesis Anastasia Pyriochou, Dimitris Beis,
Vasiliki Koika, Christos Potytarchou,
Evangelia Papadimitriou, Zongmin Zhou,
and Andreas Papapetropoulos
Role of Myocardial Nitric Oxide in Diabetic Ischemia-
Reperfusion Dysfunction: Studies in Mice with Myocyte-
Specific Overexpression of Endothelial Nitric-Oxide Synthase
Pharmacological Characterization of Novel �-Calcitonin
Gene-Related Peptide (CGRP) Receptor Peptide Antagonists
That Are Selective for Human CGRP Receptors
The Serotonin 5-Hydroxytryptaphan 1A Receptor Agonist,
(�)8-Hydroxy-2-(di-n-propylamino)-tetralin, Stimulates
Sympathetic-Dependent Increases in Venous Tone during
Hypovolemic Shock
Enhanced Thromboxane Receptor-Mediated Responses and
Impaired Endothelium-Dependent Relaxation in Human
Corpus Cavernosum from Diabetic Impotent Men: Role of
Protein Kinase C Activity
Properties of a Time-Dependent Potassium Current in Pig
Atrium: Evidence for a Role of K v1.5 in Repolarization
And Experimental Therapeutics
A Publication of the American Society for Pharmacology and Experimental Therapeutics
November 2006 Vol. 319, No. 2
The Journal of Pharmacology and Experimental Therapeutics (ISSN
0022-3565) is published monthly by the American Society for Pharmacology
and Experimental Therapeutics, 9650 Rockville Pike,
Bethesda, MD 20814-3995; email: info@aspet.org; web site:
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Contents
Beatriz Pozo-Navas, Heike Stessel,
Gerald Wölkart, and Friedrich Brunner
Christopher K. Taylor, D. David Smith,
Martin Hulce, and Peter W. Abel
914
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663
729
749
Ruslan Tiniakov and Karie E. Scrogin 776
Javier Angulo, Pedro Cuevas,
Argentina Fernández, Antonio Allona,
Ignacio Moncada, Antonio Martín-Morales,
José María La Fuente, and
Iñigo Sáenz de Tejada
Joachim R. Ehrlich, Christin Hoche,
Pierre Coutu, Christiane Metz-Weidmann,
Werner Dittrich, Stefan H. Hohnloser,
Stanley Nattel, and Heinz Gögelein
783
898
Single copy: $82.00. GST Tax Number for Canadian subscribers:
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Citation Index®, Biological Abstracts, BIOSIS Previews Database,
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American Society for Pharmacology and Experimental Therapeutics.
All rights reserved. Printed in the U.S.A.

CELLULAR AND MOLECULAR
Valproic Acid Inhibits Invasiveness in Bladder Cancer but
Not in Prostate Cancer Cells
Busulfan Selectively Induces Cellular Senescence but Not
Apoptosis in WI38 Fibroblasts via a p53-Independent but
Extracellular Signal-Regulated Kinase-p38 Mitogen-Activated
Protein Kinase-Dependent Mechanism
Nitric Oxide Production by the Vacuolar-Type (H � )-ATPase
Inhibitors Bafilomycin A1 and Concanamycin A and Its
Possible Role in Apoptosis in RAW 264.7 Cells
Determining the Potency and Molecular Mechanism of Action
of Insurmountable Antagonists
Tethered Yohimbine Analogs as Selective Human � 2C-
Adrenergic Receptor Ligands
Voltage-Gated K � Channel Block by Catechol Derivatives:
Defining Nonselective and Selective Pharmacophores
Ligands Regulate Cell Surface Level of the Human � Opioid
Receptor by Activation-Induced Down-Regulation and
Pharmacological Chaperone-Mediated Enhancement:
Differential Effects of Nonpeptide and Peptide Agonists
□S Modulation of Pro- and Antiapoptotic Molecules in Double-
Positive (CD4 � CD8 � ) Thymocytes following Dexamethasone
Treatment
Mallotoxin Is a Novel Human Ether-a-go-go-Related Gene
(hERG) Potassium Channel Activator
Prostanoid Receptors Regulate the Volume-Sensitive Efflux of
Osmolytes from Murine Fibroblasts via a Cyclic AMP-
Dependent Mechanism
CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY
Photochemical Internalization of Therapeutic Macromolecular
Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer
Cells
ENDOCRINE AND DIABETES
Transport within the Interstitial Space, Rather Than
Membrane Permeability, Determines Norepinephrine
Recovery in Microdialysis
GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
The New Low Calcemic Vitamin D Analog 22-Ene-25-Oxa-
Vitamin D Prominently Ameliorates T Helper Cell Type 1-
Mediated Colitis in Mice
Renoprotective Effects of l-Carnosine on Ischemia/
Reperfusion-Induced Renal Injury in Rats
Role of Cyclooxygenase Isoforms and Nitric-Oxide Synthase in
the Modulation of Tracheal Motor Responsiveness in Normal
and Antigen-Sensitized Guinea Pigs
Melatonin Treatment Reverts Age-Related Changes in Guinea
Pig Gallbladder Neuromuscular Transmission and
Contractility
Chien-Lun Chen, Jennifer Sung,
Michael Cohen, Wasim H. Chowdhury,
Markus D. Sachs, Ying Li,
Yegappan Lakshmanan,
Benjamin Y. M. Yung, Shawn E. Lupold,
and Ronald Rodriguez
Virginia Probin, Yong Wang, Aiping Bai,
and Daohong Zhou
JangJa Hong, Yasuhiro Nakano,
Aya Yokomakura, Kenji Ishihara,
Soonjoo Kim, Young-Sook Kang, and
Kazuo Ohuchi
Terry Kenakin, Stephen Jenkinson, and
Christian Watson
Supriya A. Bavadekar, Guoyi Ma,
Suni M. Mustafa, Bob M. Moore,
Duane D. Miller, and Dennis R. Feller
Vicenta Salvador-Recatala, Yonjung Kim,
Elena Zaks-Makhina, and Edwin S. Levitan
Yong Chen, Chongguang Chen, Yulin Wang,
and Lee-Yuan Liu-Chen
Rodolfo Bianchini, Giuseppe Nocentini,
Ludovic Tibor Krausz, Katia Fettucciari,
Stefano Coaccioli, Simona Ronchetti, and
Carlo Riccardi
Haoyu Zeng, Irina M. Lozinskaya,
Zuojun Lin, Robert N. Willette,
David P. Brooks, and Xiaoping Xu
Anne M. Heacock, Daniel J. Foster, and
Stephen K. Fisher
Pål K. Selbo, Anette Weyergang,
Anette Bonsted, Stephen G. Bown, and
Kristian Berg
H. Alec Ross, Petra J. van Gurp,
Jacques J. Willemsen,
Jacques W. M. Lenders, Cees J. Tack, and
Fred C. G. J. Sweep
Carolin Daniel, Heinfried H. Radeke,
Nico A. Sartory, Nadine Zahn,
Ulrich Zuegel, Andreas Steinmeyer, and
Jürgen Stein
Hayato Kurata, Toshihide Fujii,
Hidenobu Tsutsui, Tomoaki Katayama,
Mamoru Ohkita, Masanori Takaoka,
Nobuo Tsuruoka, Yoshinobu Kiso,
Yukihiro Ohno, Yoshihide Fujisawa,
Takatoshi Shokoji, Akira Nishiyama,
Youichi Abe, and Yasuo Matsumura
Paola Nieri, Cinzia Martinelli,
Corrado Blandizzi, Nunzia Bernardini,
Rosamiria Greco, Chiara Ippolito,
Mario Del Tacca, and Maria Cristina Breschi
Pedro J. Gomez-Pinilla,
Cristina Camello-Almaraz, Rosario Moreno,
Pedro J. Camello, and María J. Pozo
533
551
672
710
739
758
765
887
957
963
604
840
622
640
648
847

Identification of Bombesin Receptor Subtype-Specific Ligands:
Effect of N-Methyl Scanning, Truncation, Substitution, and
Evaluation of Putative Reported Selective Ligands
INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA
Effect of Transforming Growth Factor-� Receptor I Kinase
Inhibitor 2,4-Disubstituted Pteridine (SD-208) in Chronic
Allergic Airway Inflammation and Remodeling
□S A Reversible S-Adenosyl-L-Homocysteine Hydrolase Inhibitor
Ameliorates Experimental Autoimmune Encephalomyelitis by
Inhibiting T Cell Activation
Aspirin and Salicylate Suppress Polymorphonuclear Apoptosis
Delay Mediated by Proinflammatory Stimuli
Samuel A. Mantey, Nieves Gonzalez,
Michael Schumann, Tapas K. Pradhan,
Lin Shen, David H. Coy, and
Robert T. Jensen
Sum Yee Leung, Akio Niimi, Alistair Noble,
Timothy Oates, Alison S. Williams,
Satyanarayana Medicherla,
Andrew A. Protter, and Kian Fan Chung
Yun-Feng Fu, Yi-Na Zhu, Jia Ni,
Xiang-Gen Zhong, Wei Tang, Yu-Dan Re,
Li-Ping Shi, Jin Wan, Yi-Fu Yang,
Chong Yuan, Fa-Jun Nan, Brian R. Lawson,
and Jian-Ping Zuo
Soledad Negrotto, Elisa Malaver,
María Eugenia Alvarez, Natalia Pacienza,
Lina Paola D’Atri, Roberto Gabriel Pozner,
Ricardo Martín Gómez, and Mirta Schattner
METABOLISM, TRANSPORT, AND PHARMACOGENOMICS
Variability of CYP2J2 Expression in Human Fetal Tissues Andrea Gaedigk, Darren W. Baker,
Rheem A. Totah, Roger Gaedigk,
Robin E. Pearce, Carrie A. Vyhlidal,
Darryl C. Zeldin, and J. Steven Leeder
Identification of Cell Adhesion Molecules in the Human
Follicle-Associated Epithelium That Improve Nanoparticle
Uptake into the Peyer’s Patches
□S Nuclear Trafficking of a Gadolinium Conjugate in Nude Mice
Xenografted with Human LN-229 Glioma
Induction of Human CYP2A6 Is Mediated by the Pregnane X
Receptor with Peroxisome Proliferator-Activated Receptor-�
Coactivator 1�
N-Acetyltransferase (Nat) 1 and 2 Expression in Nat2
Knockout Mice
Molecular Determinants in the Transport of a Bile Acid-
Derived Diagnostic Agent in Tumoral and Nontumoral Cell
Lines of Human Liver
Increased Estrogen Sulfation of Estradiol 17�-D-Glucuronide
in Metastatic Tumor Rat Livers
Elucidating the Effect of Final-Day Dosing of Rifampin in
Induction Studies on Hepatic Drug Disposition and
Metabolism
Cisplatin and Oxaliplatin, but Not Carboplatin and
Nedaplatin, Are Substrates for Human Organic Cation
Transporters (SLC22A1–3 and Multidrug and Toxin
Extrusion Family)
Effects of Trimethoprim on the Clearance of Apricitabine, a
Deoxycytidine Analog Reverse Transcriptase Inhibitor, and
Lamivudine in the Isolated Perfused Rat Kidney
NEUROPHARMACOLOGY
A Nonfeminizing Estrogen Analog Protects against Ethanol
Withdrawal Toxicity in Immortalized Hippocampal Cells
Modafinil Occupies Dopamine and Norepinephrine
Transporters in Vivo and Modulates the Transporters and
Trace Amine Activity in Vitro
Elisabet Gullberg, Åsa V. Keita,
Sa’ad Y. Salim, Margaretha Andersson,
Karin D. Caldwell, Johan D. Söderholm, and
Per Artursson
980
586
799
972
523
632
Stefan Heckl and Ulrich Vogel 657
Masahiro Itoh, Miki Nakajima,
Eriko Higashi, Ryoko Yoshida,
Kiyoshi Nagata, Yasushi Yamazoe, and
Tsuyoshi Yokoi
Jennifer A. Loehle, Valerie Cornish,
Larissa Wakefield, Mark A. Doll,
Jason R. Neale, Yu Zang, Edith Sim, and
David W. Hein
Antonin Libra, Cristina Fernetti,
Vito Lorusso, Massimo Visigalli,
Pier Lucio Anelli, Frantisek Staud,
Claudio Tiribelli, and Lorella Pascolo
Huadong Sun, Lichuan Liu, and
K. Sandy Pang
Justine L. Lam, Sarah B. Shugarts,
Hideaki Okochi, and Leslie Z. Benet
Atsushi Yonezawa, Satohiro Masuda,
Sachiko Yokoo, Toshiya Katsura, and
Ken-ichi Inui
Tomoko Nakatani-Freshwater,
Mariana Babayeva, Aruna Dontabhaktuni,
and David R. Taft
Marianna E. Jung, Andrew M. Wilson, and
James W. Simpkins
Bertha K. Madras, Zhihua Xie,
Zhicheng Lin, Amy Jassen, Helen Panas,
Laurie Lynch, Ryan Johnson, Eli Livni,
Thomas J. Spencer, Ali A. Bonab,
Gregory M. Miller, and Alan J. Fischman
693
724
809
818
864
879
941
543
561

Dopamine Transporter (DAT) Inhibitors Alleviate Specific
Parkinsonian Deficits in Monkeys: Association with DAT
Occupancy in Vivo
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)
38 and PACAP4–6 Are Neuroprotective through Inhibition of
NADPH Oxidase: Potent Regulators of Microglia-Mediated
Oxidative Stress
Mechanism-Based Pharmacokinetic-Pharmacodynamic
Modeling of the Respiratory-Depressant Effect of
Buprenorphine and Fentanyl in Rats
The Mechanism of Carbamazepine Aggravation of Absence
Seizures
Effects of Glycogen Synthase Kinase 3� and Cyclin-
Dependent Kinase 5 Inhibitors on Morphine-Induced
Analgesia and Tolerance in Rats
Effects of Prenatal Ethanol Exposure on the Excitability of
Ventral Tegmental Area Dopamine Neurons in Vitro
Functional Selectivity of NK1 Receptor Signaling: Peptide
Agonists Can Preferentially Produce Receptor Activation or
Desensitization
Concentration-Dependent Modulation of Amyloid-� in Vivo
and in Vitro Using the �-Secretase Inhibitor, LY-450139
TOXICOLOGY
Depletion of Glutathione Induces 4-Hydroxynonenal Protein
Adducts and Hydroxyurea Teratogenicity in the
Organogenesis Stage Mouse Embryo
Levels of 4-Hydroxynonenal and Malondialdehyde Are
Increased in Brain of Human Chronic Users of
Methamphetamine
Calcineurin Activation Is Not Necessary for Doxorubicin-
Induced Hypertrophy in H9c2 Embryonic Rat Cardiac Cells:
Involvement of the Phosphoinositide 3-Kinase-Akt Pathway
System B 0,� and the Transport of Thiol-S-Conjugates of
Methylmercury
Bertha K. Madras, Michele A. Fahey,
Martin Goulet, Zhicheng Lin, Jacob Bendor,
Claudia Goodrich, Peter C. Meltzer,
David R. Elmaleh, Eli Livni, Ali A. Bonab,
and Alan J. Fischman
Sufen Yang, Jun Yang, Zhengqin Yang,
Posee Chen, Alison Fraser, Wei Zhang,
Hao Pang, Xi Gao, Belinda Wilson,
Jau-Shyong Hong, and Michelle L. Block
Ashraf Yassen, Jingmin Kan, Erik Olofsen,
Ernst Suidgeest, Albert Dahan, and
Meindert Danhof
Lige Liu, Thomas Zheng,
Margaret J. Morris, Charlott Wallengren,
Alison L. Clarke, Christopher A. Reid,
Steven Petrou, and Terence J. O’Brien
Jan Rodriguez Parkitna, Ilona Obara,
Agnieszka Wawrzczak-Bargiela,
Wioletta Makuch, Barbara Przewlocka, and
Ryszard Przewlocki
Jue Wang, Samir Haj-Dahmane, and
Roh-Yu Shen
570
595
682
790
832
857
Mark A. Simmons 907
Thomas A. Lanz, Michael J. Karmilowicz,
Kathleen M. Wood, Nikolay Pozdnyakov,
Ping Du, Mary A. Piotrowski,
Tracy M. Brown, Charles E. Nolan,
Karl E. G. Richter, James E. Finley,
Qing Fei, Charles F. Ebbinghaus,
Yuhpyng L. Chen, Douglas K. Spracklin,
Barbara Tate, Kieran F. Geoghegan,
Lit-Fui Lau, David D. Auperin, and
Joel B. Schachter
924
Jin Yan and Barbara F. Hales 613
Paul S. Fitzmaurice, Junchao Tong,
Mehrdad Yazdanpanah, Peter P. Liu,
Kathryn S. Kalasinsky, and Stephen J. Kish
Kevyn E. Merten, Youchun Jiang,
Wenke Feng, and Y. James Kang
□S Supplemental material is available online at http://jpet.aspetjournals.org.
703
934
Christy C. Bridges and Rudolfs K. Zalups 948
About the cover: Double-stained skeletons of the fetuses exposed to HU without or with BSO. See the
article by Yan and Hales on page 613 of this issue.