Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Molecular Mechanisms for Species Differences in Organic Anion Transporter 1, OAT1: Implications for Renal Drug Toxicity

Ling Zou, Adrian Stecula, Anshul Gupta, Bhagwat Prasad, Huan-Chieh Chien, Sook Wah Yee, Li Wang, Jashvant D. Unadkat, Simone H. Stahl, Katherine S. Fenner and Kathleen M. Giacomini
Molecular Pharmacology July 2018, 94 (1) 689-699; DOI: https://doi.org/10.1124/mol.117.111153
Ling Zou
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adrian Stecula
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anshul Gupta
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bhagwat Prasad
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huan-Chieh Chien
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sook Wah Yee
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Wang
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jashvant D. Unadkat
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simone H. Stahl
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine S. Fenner
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen M. Giacomini
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California (L.Z., A.S., H.-C.C., S.W.Y., K.M.G.); Pharmacokinetics and Drug Metabolism, Amgen Inc., Cambridge, Massachusetts (A.G.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (B.P., L.W., J.D.U.); and Safety and ADME Translational Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, UK (S.H.S., K.S.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • Fig. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 1.

    Species differences in the inhibition potencies of ANPs (adefovir, cidofovir, and tenofovir) for OAT1-mediated 6CF uptake. HEK293 cells stably expressing hOAT1, cyOAT1, rat OAT1, mouse OAT1, and dog OAT1 were incubated with HBSS buffer containing 6CF (1 μM) for 1 minute with or without designed concentrations of adefovir, cidofovir, and tenofovir. Data points represent the mean ± S.D. of 6CF uptake from three replicate determinations in a single experiment. The experiments were repeated three times and similar results were obtained. Representative curves of the OAT1-mediated 6CF uptake inhibition by ANPs: (A) Adefovir; (B) Cidofovir; (C) Tenofovir. The IC50 values for each of the analogs with each OAT1 ortholog are listed in Table 1.

  • Fig. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 2.

    Kinetics of uptake of tenofovir for species orthologs of OAT1. (A) The uptake kinetics of [3H]-tenofovir in HEK293 cells expressing hOAT1, cyOAT1, rat OAT1, mouse OAT1, and dog OAT1. The uptake rate was evaluated at 3 minutes. Each point represents the mean ± S.D. uptake in the OAT1-transfected cells minus that in empty vector cells. (B) Correlation of the Vmax value of OAT1-mediated tenofovir uptake in HEK293 cells stably expressing five OAT1 species orthologs with total cell membrane-bound OAT1 protein quantity (R2 = 0.892).

  • Fig. 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 3.

    Chimera proteins of OAT1 created to assess the critical domains and residues involved in the species differences of tenofovir kinetics in cells stably expressing hOAT1 and cyOAT1. (A) Predicted membrane-bound hOAT1 structure showing 550 amino acids. The white color indicates amino acid residues that are conserved between hOAT1 and cyOAT1, the turquoise color shows residues that vary between hOAT1 and cyOAT1, and the orange color indicates residues that were mutated and evaluated for tenofovir transport kinetics. (B) Wild-type hOAT1, cyOAT1, and chimeric proteins with different combinations of hOAT1 and cyOAT1 amino acids. (C) [3H]-tenofovir uptake by OAT1 chimera proteins. Transiently transfected HEK293 cells overexpressing chimera proteins were incubated with [3H]-tenofovir (50 nM) for 3 minutes. (D) [3H]-tenofovir uptake by cyOAT1 mutants (cyOAT1 S198A, A203S, I254V, and V256A) and hOAT1 mutant (hOAT1 S203A). Transiently transfected HEK293 cells overexpressing mutant proteins were incubated with [3H]-tenofovir (50 nM) for 3 minutes. (E) Eadie-Hofstee plot for the [3H]-tenofovir uptake by stable cell lines overexpressing hOAT1 and cyOAT1 and their mutants, hOAT1 S203A and cyOAT1 A203S. (F) Comparison of the averaged Km values for OAT1 orthologs with S203 (N = 7, including human, chimpanzee, gorilla, orangutan, gibbon, galago, and cynomolgus monkey OAT1 A203S) with that for OAT1 orthologs with alanine at the equivalent position (N = 6, including cynomolgus monkey, squirrel monkey, mouse, rat, dog, and human OAT1 S203A). Student’s t test was performed to determine significant differences between the two groups. (G) The uptake rate of [3H]-adefovir and [3H]-cidofovir in cells overexpressing hOAT1 and cyOAT1 and the mutants, hOAT1 S203A and cyOAT1 A203S. Each column represents the mean ± S.D. uptake in the OAT1-transfected cells minus that in empty vector cells. Two experiments were conducted and there were four replicates for each experiment. Statistical analyses were performed by one-way analysis of variance followed by Tukey’s multiple comparisons test to determine significant differences between controls and treatment groups. (H) The rate of uptake of [3H]-tenofovir in HEK293 cells overexpressing hOAT1 or cyOAT1 with or without 120-minute preincubation with 5 mM α-ketoglutarate or 5 mM glutaric acid. Each bar represents uptake (mean ± S.D.) in the OAT1-transfected cells minus that in empty vector cells (N ≥ 2). *P value <0.05; **P value < 0.01; ***P value <0.001; ****P value = 0.0001. n.s., not significant.

  • Fig. 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 4.

    Association of OAT1-mediated tenofovir transport efficiency (Vmax/Km) with SUA levels and effect of amino acid substitutions in hOAT1 on tenofovir uptake rate. (A) Mean ± S.D. of SUA levels (black bar) and OAT1-mediated tenofovir transport efficiencies (gray bar) in species with (cynomolgus monkey, squirrel monkey, mouse, rat, and dog) and without (human, chimpanzee, gorilla, orangutan, and gibbon) functional uricase (* represents comparison of SUA levels in species with and without uricase; # represents comparison of tenofovir transport efficiencies in species with and without uricase; **P < 0.01; ####P < 0.0001). (B) [3H]-tenofovir uptake by hOAT1, cyOAT1, and mutants (hOAT1 S203T and hOAT1 S203A). Transiently transfected HEK293 cells overexpressing wild-type or mutant proteins were incubated with [3H]-tenofovir (50 nM) for 3 minutes. Transporter-mediated tenofovir uptake was obtained after subtracting the respective rate of uptake in empty vector cells.

  • Fig. 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 5.

    Uric acid uptake in HEK293 cells expressing hOAT1 or cyOAT1 as a function of time and concentration. (A) Uptake of [14C]-uric acid (20 μM) as a function of time in cells expressing hOAT1 and in empty vector cells. (B) Kinetics of [14C]-uric acid uptake by hOAT1 and cyOAT1. HEK293 cells overexpressing hOAT1 and cyOAT1 were incubated with [14C]-uric acid (20 μM) with various concentrations of unlabeled uric acid for 5 minutes. Stock of uric acid was dissolved in 0.1 N NaOH and added to obtain designed concentrations in HBSS buffer plus 10 mM HEPES to maintain pH 7.4. Each point represents the uptake in OAT1-expressing cells minus that in empty vector cells.

Tables

  • Figures
  • Additional Files
    • View popup
    TABLE 1

    Potencies of ANPs in inhibiting 6CF uptake by OAT1 species orthologs from human, cynomolgus monkey, mouse, rat, and dog

    Statistical analyses were performed by one-way analysis of variance followed by Dunnett’s multiple comparisons test. N ≥ 2.

    InhibitorIC50
    HumanCynomolgus MonkeyMouseRatDog
    μMμMμMμMμM
    Adefovir71 ± 15220 ± 67*399 ± 147***263 ± 66*181 ± 4
    Cidofovir88 ± 25181 ± 67237 ± 69**245 ± 19**185 ± 27
    Tenofovir61 ± 14343 ± 40****165 ± 27*153 ± 17223 ± 64**
    • ↵* P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

    • View popup
    TABLE 2

    Kinetic parameters of the tenofovir uptake by OAT1 species orthologs from human, cynomolgus monkey, mouse, rat, and dog

    Statistical analyses were performed by one-way analysis of variance followed by Dunnett’s multiple comparisons test. N ≥ 2; &, tenofovir transport efficiency for OAT1 from each species was normalized to the corresponding membrane-bound OAT1 quantity (Supplemental Table 3).

    ParameterHumanCynomolgus MonkeyMouseRatDog
    Km (μM)72.6 ± 20254 ± 0.1****138 ± 18***139 ± 7.6***157 ± 8.8****
    Vmax (nmol/mg/min)4.6 ± 1.42.5 ± 0.22.4 ± 0.6*2.1 ± 0.6*3.9 ± 0.9
    Vmax/Km (μl/mg/min)6310171525
    Normalized Vmax/Km (μl/mg/min)&1.620.471.172.590.88
    • ↵* P < 0.05; ***P < 0.001; ****P < 0.0001.

    • View popup
    TABLE 3

    Kinetic parameters for OAT1-mediated uptake by wild-type and mutant transporters

    Mutations were created by site-directed mutagenesis of both hOAT1 and cyOAT1 at position 203. Statistical analyses were performed by one-way analysis of variance followed by Tukey’s multiple comparisons test. N ≥ 2; * represents comparison with human; # represents comparison between cynomolgus monkey and cynomolgus monkey A203S.

    ParameterHumanCynomolgus MonkeyCynomolgus Monkey A203SHuman S203A
    Km (μM)72.6 ± 20254 ± 0.1****105 ± 27###216 ± 19***
    Vmax (nmol/mg/min)4.6 ± 1.42.5 ± 0.22.8 ± 0.13.6 ± 0.7
    Vmax/Km (μl/mg/min)63102717
    • ↵*** P < 0.001; ****P < 0.0001; ###P < 0.001.

    • View popup
    TABLE 4

    Kinetic parameters of tenofovir uptake rate by OAT1 wild-type transporters and mutants at position 203

    SpeciesAmino Acid at position 203 or Equivalent PositionKm
    μM
    HumanS72.6 ± 20
    ChimpanzeeS44.2 ± 1.5
    GorillaS56.0 ± 7.5
    OrangutanS79.0 ± 16
    GibbonS65.0 ± 2.4
    GalagoS84.9 ± 24
    cyOAT1 A203SS105 ± 27
    Cynomolgus monkeyA254 ± 0.1
    Squirrel monkeyA181 ± 60
    MouseA138 ± 18
    RatA139 ± 7.6
    DogA157 ± 8.8
    hOAT1 S203AA216 ± 19
    • S, Serine; A, Alanine.

    • View popup
    TABLE 5

    OAT1-mediated tenofovir transport efficiencies and SUA levels in species with or without functional uricase

    *The mean value of SUA was calculated based on reported levels. The range of SUA is included in parenthesis. —, not applicable.

    SpeciesWithout Uricase ActivityWith Uricase Activity
    SUA*Tenofovir Transport EfficiencySUATenofovir Transport Efficiency
    μMμl/mg/minμMμl/mg/min
    Human318 (210–420) (Tan et al., 2016)63——
    Chimpanzee244 (120–360) (Fanelli and Beyer, 1974)61——
    Gorilla146 (130–160) (Fanelli and Beyer, 1974)49——
    Orangutan140 (110–170) (Fanelli and Beyer, 1974)69——
    Gibbon178 (120–300) (Fanelli and Beyer, 1974)52——
    Cynomolgus monkey——36 (30–42) (Fanelli and Beyer, 1974)10
    Squirrel monkey——30 (12–60) (Fanelli and Beyer, 1974)15
    Mouse——53 (30–78) (Wu et al., 1994; So and Thorens, 2010)17
    Rat——67 (64–70) (Mazzali et al., 2001; Lu et al., 2016)15
    Dog——18 (Miller et al., 1951)25
    Mean205 ± 7558.9 ± 8.341 ± 1916.5 ± 5.3
    • View popup
    TABLE 6

    Kinetic parameters of [14C]-uric acid uptake by hOAT1 and cyOAT1 in HEK293 cells stably expressing the transporters

    Student’s t test was performed to determine significant differences between the two groups. N ≥ 2.

    ParameterHumanCynomolgus Monkey
    Km (μM)571 ± 97.71070 ± 90**
    Vmax (pmol/mg/min)1510 ± 2431040 ± 106
    Vmax/Km (μl/mg/min)2.60.97
    • ↵** P < 0.01.

Additional Files

  • Figures
  • Tables
  • Data Supplement

    • Supplemental Data -

      Supplemental Figure 1 - Molecular model of the interaction of tenofovir with serine at the position 203 of hOAT1

      Supplemental Figure 2 - Kinetics of PAH uptake by hOAT1 and cyOAT1

      Supplemental Figure 3 - Correlation of serum uric acid concentration with tenofovir transport efficiency for OAT1

      Supplemental Figure 4 - Regional plot of the SLC22A6 locus

      Supplemental Table 1 - Primers

      Supplemental Table 2 - Amino acid sequence identity between hOAT1 and orthologs from cynomolgus monkey, mouse, rat and dog

      Supplemental Table 3 - Quantification of membrane-bound OAT1 protein in stable cell lines and kidney cortex from human, cynomolgus monkey, mouse, rat and dog

      Supplemental Table 4 - List of the amino acid at position 203 in hOAT1 and the equivalent position in OAT1 orthologs from primates and more distant species

      Supplemental Table 5 - Kinetic parameters of PAH uptake by hOAT1 and cyOAT1

      Supplemental Table 7 - Summary of statistical analysis results for Table 1, Table 2, Table 3 and Table 6

    • Supplemental Table 6 -

      Allele frequency of each populations in 1000 genomes

PreviousNext
Back to top

In this issue

Molecular Pharmacology: 94 (1)
Molecular Pharmacology
Vol. 94, Issue 1
1 Jul 2018
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Molecular Mechanisms for Species Differences in Organic Anion Transporter 1, OAT1: Implications for Renal Drug Toxicity
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

OAT1 in Antiviral Drug-Induced Renal Toxicity

Ling Zou, Adrian Stecula, Anshul Gupta, Bhagwat Prasad, Huan-Chieh Chien, Sook Wah Yee, Li Wang, Jashvant D. Unadkat, Simone H. Stahl, Katherine S. Fenner and Kathleen M. Giacomini
Molecular Pharmacology July 1, 2018, 94 (1) 689-699; DOI: https://doi.org/10.1124/mol.117.111153

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

OAT1 in Antiviral Drug-Induced Renal Toxicity

Ling Zou, Adrian Stecula, Anshul Gupta, Bhagwat Prasad, Huan-Chieh Chien, Sook Wah Yee, Li Wang, Jashvant D. Unadkat, Simone H. Stahl, Katherine S. Fenner and Kathleen M. Giacomini
Molecular Pharmacology July 1, 2018, 94 (1) 689-699; DOI: https://doi.org/10.1124/mol.117.111153
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics