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Molecular Pharmacology

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Research ArticleArticle

A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation

Scott Earley, Albert L. Gonzales and Zarine I. Garcia
Molecular Pharmacology April 2010, 77 (4) 612-620; DOI: https://doi.org/10.1124/mol.109.060715
Scott Earley
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Albert L. Gonzales
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Zarine I. Garcia
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Abstract

The Mediterranean diet may be responsible for lower cardiovascular disease rates in Southern versus Northern European countries. Oregano is used abundantly in Mediterranean cooking, but potential cardiovascular benefits have not been investigated. Carvacrol, present in oregano, activates the transient receptor potential (TRP) cation channels TRPA1 and TRPV3. We hypothesized that chemosensing of this dietary molecule by TRP channels in the endothelium promotes arterial relaxation. TRPA1 and TRPV3 were detected in the endothelium of intact arteries. Carvacrol causes concentration-dependent increases in the intracellular [Ca2+] of native cerebral artery endothelial cells and is more potent (EC50 = 34 μM) than the TRPA1 agonist allyl isothiocyanate (EC50 = 400 μM) or the TRPV3 agonist eugenol (EC50 = 2.3 mM). Carvacrol also activates TRPV3-like cation currents in cerebral artery endothelial cells. Carvacrol elicits vasodilation of intact cerebral arteries (EC50 = 4.1 μM) that is accompanied by smooth muscle hyperpolarization and a decrease in the intracellular [Ca2+] of arterial myocytes. Endothelium disruption inhibits carvacrol-induced vasodilation, but block of nitric-oxide synthase and cyclooxygenase activity does not alter the response. Vasodilation in response to carvacrol is inhibited when blockers of Ca2+-activated K+ channels are present in the lumen or when the inwardly rectifying K+ channel blocker BaCl2 is present in the superfusion bath. Carvacrol-induced dilation is not diminished by a TRPA1 antagonist but is inhibited by the TRPV blocker ruthenium red. Our findings show that oregano can relax arteries by activating TRPV3 channels in the endothelium. This effect may account for some of the cardioprotective effects of the Mediterranean diet.

Footnotes

    fn-1
  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • fn-2
  • This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grants R01-HL091905, F31-HL094145]; and the American Heart Association [Grant AHA0535226N].

  • fn-3
  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.109.060715.

  • fn-4
  • ABBREVIATIONS:

    TRP
    transient receptor potential
    TRPV
    vanilloid transient receptor potential
    TRPA
    ankyrin transient receptor potential
    AITC
    allyl isothiocyanate
    IKCa
    intermediate conductance Ca2+-activated K+ channel
    SKCa
    small-conductance Ca2+-activated K+ channel
    eNOS
    endothelial nitric-oxide synthase
    IEL
    internal elastic lamina
    l-NNA
    Nω-nitro-l-arginine
    COX
    cyclooxygenase
    KIR
    inwardly rectifying K+ channel
    RuR
    ruthenium red
    NOS
    nitric-oxide synthase
    PSS
    physiological saline solution
    AM
    acetoxymethyl ester
    PCR
    polymerase chain reaction
    RT-PCR
    reverse transcriptase-polymerase chain reaction
    MOPS
    3-(N-morpholino)propanesulfonic acid
    HC-030031
    2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide.

    • Received August 31, 2009.
    • Accepted January 19, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 77 (4)
Molecular Pharmacology
Vol. 77, Issue 4
1 Apr 2010
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Research ArticleArticle

A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation

Scott Earley, Albert L. Gonzales and Zarine I. Garcia
Molecular Pharmacology April 1, 2010, 77 (4) 612-620; DOI: https://doi.org/10.1124/mol.109.060715

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Research ArticleArticle

A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation

Scott Earley, Albert L. Gonzales and Zarine I. Garcia
Molecular Pharmacology April 1, 2010, 77 (4) 612-620; DOI: https://doi.org/10.1124/mol.109.060715
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