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Research ArticleCARDIOVASCULAR

Serotonin Receptors in Rat Jugular Vein: Presence and Involvement in the Contraction

A. Elizabeth Linder, Geri L. Gaskell, Theodora Szasz, Janice M. Thompson and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics July 2010, 334 (1) 116-123; DOI: https://doi.org/10.1124/jpet.109.163014
A. Elizabeth Linder
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Geri L. Gaskell
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Theodora Szasz
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Janice M. Thompson
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Stephanie W. Watts
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Abstract

Serotonin (5-hydroxytryptamine; 5-HT) is released during platelet aggregation, a phenomenon commonly observed in blood clot formation and venous diseases. Once released, 5-HT can interact with its receptors in the peripheral vasculature to modify vascular tone. The goal of this study was to perform a detailed pharmacological characterization of the 5-HT receptors involved in the contractile response of the rat jugular vein (RJV) using recently developed drugs with greater selectivity toward 5-HT receptor subtypes. We hypothesized that, as for other blood vessels, the 5-HT1B/1D and 5-HT2B receptor subtypes mediate contraction in RJV alongside the 5-HT2A receptor subtype. Endothelium-intact RJV rings were set up in an isolated organ bath for isometric tension recordings, and contractile concentration-effect curves were obtained for 13 distinct serotonergic receptor agonists. Surprisingly, the 5-HT1A and the mixed 5-HT1A/1B receptor agonists (±)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969) caused contractions that were antagonized by the 5-HT1A receptor antagonist [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100135). The contractile curve to 5-HT was shifted to the right by WAY100135, 3-[2-[4-(4-fluoro benzoyl)-piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione (ketanserin; 5-HT2A/C receptor antagonist), and 1-(2-chloro-3,4-dimethoxybenzyl)-6-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole hydrochloride (LY266097; 5-HT2B receptor antagonist). Ketanserin also caused rightward shifts of the contractile curves to 8-OH-DPAT, RU24969, and the 5-HT2B receptor agonist (α-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine) (BW723C86). Agonists for 5-HT1B/1D/1F, 5-HT3, 5-HT6, and 5-HT7 receptors were inactive. In real-time polymerase chain reaction experiments that have never been performed in this tissue previously, we observed mRNA expression for the 5-HT2A, 5-HT2B, and 5-HT7 receptors, whereas no significant mRNA expression was found for 5-HT1A, 5-HT1B, and 5-HT1D receptors. These results support the 5-HT2A receptor as the main subtype targeted by 5-HT to contract the RJV.

Footnotes

  • This work was supported in part by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant 81115] (to S.W.W.) and Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina and Conselho Nacional de Desenvolvimento Científico e Tecnológico [Grant 2371/090] (to A.E.L.). A.E.L. was a recipient of an American Heart Association Postdoctoral Fellowship [Grant 0725729Z].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.163014.

  • ABBREVIATIONS:

    5-HT
    5-hydroxytryptamine (serotonin)
    DOI
    (±)-2,5-dimethoxy-(−)4-iodo-2,5-dimethoxyphenylisopropylamine
    PCR
    polymerase chain reaction
    PGF2α
    prostaglandin F2α
    8-OH-DPAT
    (±)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene
    RU24696
    5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole)
    5-CT
    5-carboxamidotryptamine
    BRL54443
    5-hydroxy-3-(1-methylpiperidin-4-yl)-1H-indole
    BW723C86
    α-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine
    EMD386088
    5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride
    LP44
    4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide hydrochloride
    WAY100135
    [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
    GR127935
    2-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic-acid[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]amide
    LY266097
    (1-(2-chloro-3,4-dimethoxybenzyl)-6-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole hydrochloride)
    SB269970
    (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-mentyl-1-piperidinyl)ethyl] pyrrolidine hydrochloride
    β2m
    β-2-microglobulin
    Ct
    cycle threshold.

  • Received October 26, 2009.
  • Accepted April 7, 2010.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
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Research ArticleCARDIOVASCULAR

Serotonin Receptors in Rat Jugular Vein: Presence and Involvement in the Contraction

A. Elizabeth Linder, Geri L. Gaskell, Theodora Szasz, Janice M. Thompson and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics July 1, 2010, 334 (1) 116-123; DOI: https://doi.org/10.1124/jpet.109.163014

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Research ArticleCARDIOVASCULAR

Serotonin Receptors in Rat Jugular Vein: Presence and Involvement in the Contraction

A. Elizabeth Linder, Geri L. Gaskell, Theodora Szasz, Janice M. Thompson and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics July 1, 2010, 334 (1) 116-123; DOI: https://doi.org/10.1124/jpet.109.163014
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