The Journal of
PHARMACOLOGY
And Experimental Therapeutics
A Publication of the American Society for Pharmacology and Experimental Therapeutics
October 2004
Vol. 311, No. 1
Contents
ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION
Multiple Novel Nonsynonymous CYP2B6 Gene Polymorphisms
Thomas Lang, Kathrin Klein, Tanja Richter,
in Caucasians: Demonstration of Phenotypic Null Alleles
Arne Zibat, Reinhold Kerb,
Michel Eichelbaum, Matthias Schwab, and
Ulrich M. Zanger
GHB (y-Hydroxybutyrate) Carrier-Mediated Transport across
the Blood-Brain Barrier
Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3)
to the Hepatic Uptake of Pitavastatin in Humans
Gemfibrozil and Its Glucuronide Inhibit the Organic Anion
Transporting Polypeptide 2 (OATP2/OATP1B1:SLC2JA6)Mediated Hepatic Uptake and CYP2C8-Mediated Metabolism
of Cerivastatin: Analysis of the Mechanism of the Clinically
Relevant Drug-Drug Interaction between Cerivastatin and
Gemfibrozil
Indranil Bhattacharya and
Kathleen M. K. Boje
Masaru Hirano, Kazuya Maeda, Yoshihisa
Shitara, and Yuichi Sugiyama
Yoshihisa Shitara, Masaru Hirano,
Hitoshi Sato, and Yuichi Sugiyama
34
92
139
228
Pharmacokinetics of Erythromycin in Rabbit Corneas after
Single-Dose Infusion: Role of P-Glycoprotein as a Barrier to in
Vivo Ocular Drug Absorption
Surajit Dey, Sriram Gunda, and
Ashim K. Mitra
246
Effect of Quinidine on the 10-Hydroxylation of fi-Warfarin:
Species Differences and Clearance Projection
Qing Chen, Eugene Tan, John R. Strauss,
Zhoupeng Zhang, Judith E. Fenyk-Melody,
Catherine Booth-Genthe, Thomas H.
Rushmore, Ralph A. Stearns, David C.
Evans, Thomas A. Baillie, and Wei Tang
307
XP13512 [(±)-l-([(a-Isobutanoyloxyethoxy)carbonyl]aniinomethyl)1-cyclohexane Acetic Acid], A Novel Gabapcntin Prodrug: I.
Design, Synthesis, Enzymatic Conversion to Gabapentin, and
Transport by Intestinal Solute Transporters
XP13512 [(±)-l-([(a-Isobutanoyloxyethoxy)carbonyl]aminomethyl)
1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug:
II. Improved Oral Bioavailability, Dose Proportionality, and
Colonic Absorption Compared with Gabapentin in Rats
and Monkeys
,
Kenneth C. Cundy, Russell Branch, Tania
Chernov-Rogan, Tracy Dias, Tono
Estrada, Karin Hold, Kerry Koller, Xiaoli
Liu, Adam Mann, Matt Panuwat, Stephen
P. Raillard, Shubhra Upadhyay, Quincey
Q. Wu, Jia-Ning Xiang, Hui Yan, Noa
Zerangue, Cindy X. Zhou, Ronald W.
Barrett, and Mark A. Gallop
Kenneth C. Cundy, Thamil Annamalai, Lin
Bu, Josephine De Vera, Jenny Estrela,
Wendy Luo, Payal Shirsat, Allan Torneros,
Fenmei Yao, Joan Zou, Ronald W. Barrett,
mdMfli'kA.iGallop
315
324
BEHAVTORAL PHARMACOLOGY
Antiallodynic Effects of Loperamide and Fentanyl against
Topical Capsaicin-Induced Allodynia in Unanesthetized
Primates
Antinociceptive Structure-Activity Studies with EnkephalinBased Opioid Glycopeptides
CARDIOVASCULAR
iV-Methyi-D-aspartate Receptor Blockade Inhibits Cardiac
Inflammation in the Mg2+-Deficient Rat
The Protective Effect of Superoxide Dismutase Mimetic
M40401 on Balloon Injury-Related Neointima Formation: Role
of the Lectin-Like Oxidized Low-Density Lipoprotein
Receptor-1
Regulation of Gene Expression in Cardiomyocytes by Thyroid
Hormone and Thyroid Hormone Analogs 3,5Diiodothyropropionic Acid and CGS 23425 [iV-[3,5-Dimetliyl4-(4'-hydroxy-3'-isopropylphenoxy)-phenyl]-oxamic Acid]
Pharmacology of the Urotensin-II Receptor Antagonist
Palosuran (ACT-058362; l-[2-(4-Benzyl-4-hydroxy-piperidin-lyl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea Sulfate Salt): First
Demonstration of a Pathophysiological Role of the Urotensin
System
Characterization of Cannabinoid Modulation of Sensory
Neurotransmission in the Rat Isolated Mesenteric Arterial
Bed
Effects of Pravastatin on the Expression of ATP-Binding
Cassette Transporter Al
CELLULAR AND MOLECULAR
p53-Dependent Apoptotic Mechanism of a New Designer
Bimetallic Compound Tri-phenyl Tin Benzimidazolethiol
Copper Chloride (TPT-CuCI2): In Vivo Studies in Wistar Rats
as Well as in Vitro Studies in Human Cervical Cancer Cells
Identification of Amino Acid Residues Involved in the
Inactivation of Cytochrome P450 2B1 by Two Acetylenic
Compounds: The Role of Three Residues in Nonsubstrate
Recognition Sites
Insulin Signaling Regulates y-Glutamyleysteine Ligase
Catalytic Subunit Expression in Primary Cultured Rat
Hepatocytes
Fenofibrate Impairs Rat Mitochondrial Function by Inhibition
of Respiratory Complex I
Domain Swapping in the Human Histamine H, Receptor
Ligand-Directed Functional Heterogeneity of Histamine H,
Receptors: Novel Dual-Function Ligands Selectively Activate
and Block H rMediated Phospholipase C and Adenylyl Cyclase
Signaling
Eduardo R. Butelman, Todd J. Harris, and
Mary Jeanne Kreek
155
Nura O. Elmagbari, Richard D. Egleton,
Michael M. Palian, John J. Lowery,
Wendi R. Schmid, Peg Davis,
Edita Navratilova, Muthu Dhanasekaran,
Charles M. Keyari, Henry I. Yamarnura,
Frank Porreca, Victor J. Hruby, Robin Polt,
and Edward J. Bilsky
290
M. Isabel Tejero-Taldo,
8
Joanna J. Chmielinska, Grace Gonzalez, I.
Tong Mak, and William B. Weglicki
Carolina Muscoli, Iolanda Sacco,
Wanessa Alecce, Ernesto Palma,
Robert Nisticb, Nicola Costa,
Fabrizio Clementi, Domenicantonio Rotiroti,
Francesco Romeo, Daniela Salvemini,
Jawahar L. Mchta, and Vincenzo Mollace
Cynthia Adamson, Niranjan Maitra,
Joseph Bahl, Kevin Greer, Scott Klcwer,
James Hoying, and Eugene Morkin
Martine Clozel, Christoph Binkert,
Magdalena Birker-Robaczewska,
Celine Boukhadra, Shuang-Shuang Ding,
Walter Fischli, Patrick Hess, Boris Mathys,
Keith Morrison, Celia Miiller, Claus Miiller,
Oliver Nayler, Changbin Qiu, Markus Rey,
Michael W. Scherz, Jorg Velker,
Thomas Weller, Jian-Fei Xi, and
Patrick Ziltener
Marnie Duncan, David A. Kendall, and
Vera Ralevic
44
164
204
411
Hitoshi Ando, Shuichi Tsuruoka,
Hisashi Yamamoto, Toshinari Takamura,
Shuichi Kaneko, and Akio Fujimura
420
Naseruddin Hod, De-e Zhu, Zhiyin Song,
Zhengsheng Wu, Sartaj Tabassum, and
Mian Wu
22
Linda B. Von Weymarn, Chitra Sridar, and
Paul F. Hollenberg
71
Sang K. Kim, Kimberley J. Woodcroft,
Sarah S. Khodadadeh, and
Raymond F. Novak
Barbara Brunmair, Andrea Lest,
Katrin Staniek, Florian Gras, Nicole Scharf,
Michael Roden, Hans Nohl,
Werner Waldhausl, and Clemens Fiirnsinn
99
109
Remko A. Bakker, Guido Dees,
Juan J. Carriilo, Raymond G. Booth, Juan F.
Lopez-Gimenez, Graeme Milligan, Philip G.
Strange, and Rob Leurs
131
Nader H. Moniri, Dawn Covington-Strachan,
and Raymond G. Booth
274
CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY
Kaurene Diterpene Induces Apoptosis in Human Leukemia
Cells Partly through a Caspase-8-Dependent Pathway
Intratumoral Administration of Methotrexate Bound to
Activated Carbon Particles: Antitumor Effectiveness against
Human Colon Carcinoma Xenografts and Acute Toxicity in
Mice
GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
Interleukin 1/3-Induced Production of H2O2 Contributes to
Reduced Sigmoid Colonic Circular Smooth Muscle
Contractility in Ulcerative Colitis
Masuo Kondoh, Ikue Suzuki, Masao Sato,
Fumihiro Nagashima, Siro Simizu,
Motoki Harada, Makiko Fujii,
Hiroyuki Osada, Yoshinori Asakawa, and
Yoshiteru Watanabe
Yuen Nakase, Akeo Hagiwara, Syuichi Kin,
Ken-ichirou Fukuda, Tadao Ito,
Tsuyoshi Takagi, Jyunshin Fujiyama,
Chohei Sakakura, Eigo Otsuji, and
Hisakazu Yamagishi
Weibiao Cao, Matthew D. Vrees,
Fabio M. Potenti, Karen M. Harnett,
Claudio Fiocchi, and Victor E. Pricolo
115
382
60
The Modulating Role of Nuclear Factor-/dt in the Action of
a7-Nicotinic Acetyteholine Receptor and Cross-Talk between
5-Lipoxygenase and CycIooxygenase-2 in Colon Cancer
Growth Induced by 4-(iV-Methyl-iV-nitrosamino)-l-{3-pyridyl)1-butanone
Yi N. Ye, Edgar S. L. Liu, Vivian Y. Shin,
William K. K. Wu, and Chi H. Cho
123
Effect of Omeprazole on Gastric Adenosine A2 and A2A
Receptor Gene Expression and Function
Linda Yip, Henry Chi Hang Leung, and
Yin Nam Kwok
180
Effect of Prolyl Endopeptidase on Digestive-Resistant Gliadin
Peptides in Vivo
Justin L. Piper, Gary M. Gray, and
Chaitan Khosla
213
Regulation of Rat Hepatocyte Function by P2Y Receptors:
Focus on Control of Glycogen Phosphorylase and Cyclic AMP
by 2-Methylthioadenosine 5'-Diphosphate
C. Jane Dixon, John F. Hall, Tania E. Webb,
and Michael R. Boarder
334
Charles S. Bockman, Michael R. Bruchas,
Wanyun Zeng, Kelly A. O'Connell, Peter
W. Abel, Margaret A. Scofield, and Frank J.
Dowd
364
Marcio A. F. de Godoy,
Ana Maria de Oliveira, and Satish Rattan
394
Atsufumi Kawabata, Satoko Kubo,
Tsuyoshi Ishiki, Naoyuki Kawao, Fumiko
Sekiguchi, Ryotaro Kuroda, Morley D.
Hollenberg, Toru Kanke, and Naohiro Saito
402
Alfredo Vannacci, Lucia Giannini,
Maria Beatrice Passani,
Annamaria Di Felice, Simone Pierpaoli,
Giovanni Zagli,
Ornella Fantappie, Roberto Mazzanti,
Emanuela Masini, and
Pier Francesco Mannaioni
256
Submandibular Gland Acinar Cells Express Multiple a xAdrenoceptor Subtypes
Angiotensin II-Induced Relaxation of Anococcygeus Smooth
Muscle via Desensitization of ATj Receptor, and Activation of
AT2 Receptor Associated with Nitric-Oxide Synthase Pathway
Proteinase-Activated Receptor-2-Mediated Relaxation in
Mouse Tracheal and Bronchial Smooth Muscle: Signal
Transduction Mechanisms and Distinct Agonist Sensitivity
INFLAMMATION AND IMMUNOPHARMACOLOGY
The Endocannabinoid 2-Arachidonylglycerol Decreases the
Immunological Activation of Guinea Pig Mast Cells:
Involvement of Nitric Oxide and Eicosanoids
NEUROPHARMACOLOGY
Methamphetamine Neurotoxicity in Dopamine Nerve Endings
of the Striatum Is Associated with Microglial Activation
The ./V-Methyl-D-aspartate Receptor Inhibitory Potencies of
Aromatic Inhaled Drugs of Abuse: Evidence for Modulation
by Cation-7r Interactions
Serofendic Acid, a Sulfur-Containing Diterpenoid Derived
from Fetal Calf Serum, Attenuates Reactive Oxygen SpeciesInduced Oxidative Stress in Cultured Striatal Neurons
Electrophysiological, Pharmacological, and Molecular
Evidence for a7-Nicotinic Acetylcholine Receptors in Rat
Midbrain Dopamine Neurons
■y-Hydroxybutyrate Increases a Potassium Current and
Decreases the H-Current in Hippocampal Neurons via
GABAB Receptors
David M. Thomas, Paul D. Walker,
1
Joyce A. Benjamins, Timothy J. Geddes, and
Donald M. Kuhn
Douglas E. Raines, Fredrick Gioia,
Robert J. Claycomb, and Renna J. Stevens
14
Fumitaka Osakada, Yuka Kawato,
Toshiaki Kume, Hiroshi Katsuki,
Hachiro Sugimoto, and Akinori Akaike
51
Jie Wu, Andrew A. George,
Katherine M. Schroeder, Lin Xu, Syndia MarxerMiller, Linda Lucero, and Ronald J. Lukas
Paul Schweitzer, Marisa Roberto,
Samuel G. Madamba, and
George Robert Siggins
80
172
The Serotonin1A Receptor Partial Agonist S15535 [4(Benzodioxan-5-yl)l-(indan-2-yl)piperazine] Enhances
Cholinergic Transmission and Cognitive Function in Rodents:
A Combined Neurochemical and Behavioral Analysis
Antiepileptic Drug Treatment of Nonconvulsive Seizures
Induced by Experimental Focal Brain Ischemia
/3-Estradiol, Dehydroepiandrosterone, and
Dehydroepiandrosterone Sulfate Protect against iV-Methyl-Daspartate-Induced Neurotoxicity in Rat Hippocampal Neurons
by Different Mechanisms
Chronic Morphine Treatment Alters A'-Methyl-D-aspartate
Receptors in Freshly Isolated Neurons from Nucleus
Accumbens
Ethanol Suppression of Ventral Tegmental Area GABA
Neuron Electrical Transmission Involves A'-Methyl-D-aspartate
Receptors
Negative Feedback Regulation of Nigrostriatal Dopamine
Release: Mediation by Striatal Dl Receptors
Short-Term Cocaine Treatment Causes Neuroadaptive
Changes in Gaq and G«n Proteins in Rats Undergoing
Withdrawal
Intrathecal Protease-Activated Receptor Stimulation Produces
Thermal Hyperalgesia through Spinal Cyclooxygenase Activity
Edaravone Protects against Hypoxia/Ischemia-Induced
Endoplasmic Reticulum Dysfunction
TOXICOLOGY
Expression and Induction of Cytochromes P450 in Rat White
Adipose Tissue
Thioether Metabolites of 3,4-Methylenedioxyamphetamine and
3,4-Methylenedioxymethamphetamine Inhibit Human
Serotonin Transporter (hSERT) Function and Simultaneously
Stimulate Dopamine Uptake into hSERT-Expressing SK-NMC Cells
Development of a Real-Time Polymerase Chain ReactionBased Method for the Measurement of Relative Allelic
Expression and Identification of CYP2A13 Alleles with
Decreased Expression in Human Lung
Mark J. Millan, Alain Gobert, Sylvain Roux,
Roger Porsolt, Alfredo Meneses,
Mirjana Carli, Benjamin Di Cara,
Robert Jaffard, Jean-Michel Rivet,
Pierre Lestage, Elisabeth Mocaer,
Jean-Louis Peglion, and Anne Dekeyne
A. J. Williams, F. C. Tortella, X. M. Lu,
J. E. Moreton, and J. A. Hartings
190
220
Kenichi Kurata, Minoru Takebayashi,
Shigeru Morinobu, and Shigeto Yamawaki
237
Gilles Martin, Ana Guadano-Ferraz,
Beatriz Morte, Serge Ahmed, George F.
Koob, Luis de Lecea, and George R. Siggins
265
Sarah H. Stobbs, Allison J. Ohran,
Matthew B. Lassen, David W. Allison, J.
Elliott Brown, and Scott C. Steffensen
282
Sanjida S. Saklayen, Omar S. Mabrouk, and
Elizabeth A. Pehek
342
Gonzalo A. Carrasco,
Katerina J. Damjanoska,
Deborah N. D'Souza, Yahong Zhang,
Francisca Garcia, George Battaglia,
Nancy A. Muma, and Louis D. Van de Kar
349
Lee Koetzner, Joshua A. Gregory, and
Tony L. Yaksh
356
Xin Qi, Yasunobu Okuma, Torn Hosoi, and
Yasuyuki Nomura
388
Kouichi Yoshinari, Takeshi Sato,
Nao Okino, Junko Sugatani, and
Masao Miwa
147
Douglas C. Jones, Serrine S. Lau, and
Terrence J. Monks
298
Xiuling Zhang, Michele Caggana,
Tracey L. Cutler, and Xinxin Ding
373