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Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling | Journal of Pharmacology and Experimental Therapeutics

<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//securepubads.g.doubleclick.net" /> <link rel="dns-prefetch" href="//cdn.jsdelivr.net" /> <link rel="dns-prefetch" href="//www.google.com" /> <link rel="dns-prefetch" href="//www.googletagmanager.com" /> <link rel="dns-prefetch" href="//cdn.foxycart.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortlink" href="/node/38288" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <meta name="article_thumbnail" content="https://jpet.aspetjournals.org/content/jpet/297/1/88/embed/mml-math-1.mml" /> <meta name="issue_cover_image" content="https://jpet.aspetjournals.org/sites/default/files/highwire/jpet/297/1.cover.gif" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/jpet/297/1/88.atom" /> <meta name="HW.pisa" content="jpet;297/1/88" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling" /> <meta name="DC.Date" content="2001-04-01" /> <meta name="DC.Publisher" content="American Society for Pharmacology and Experimental Therapeutics" /> <meta name="DC.Rights" content="The American Society for Pharmacology and Experimental Therapeutics" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="The purpose of this study was to characterize pharmacologically the 5-HT receptor(s) mediating contraction in the mouse aorta and the pathways these receptors are coupled with to mediate contraction. We hypothesized that a 5-HT2A receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT2A receptor agonist 伪-methyl-5-HT, and partial 5-HT2A receptor agonist (卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (卤-DOI) caused the most potent and efficacious contraction. The 5-HT1E/1F receptor agonist BRL 54443 also induced contraction (鈭抣og EC50 = 6.52); however, the 5-HT2A receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT2A receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT2A receptor of the rat and the data generated in our experiments (鈭抣og EC50 and p K B values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenyl N , N -diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT2A receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases." /> <meta name="DC.Contributor" content="C. M. McKune" /> <meta name="DC.Contributor" content="S. W. Watts" /> <meta name="article:published_time" content="2001-04-01" /> <meta name="article:section" content="CARDIOVASCULAR" /> <meta name="citation_title" content="Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling" /> <meta name="citation_abstract" lang="en" content="&lt;p&gt;The purpose of this study was to characterize pharmacologically the 5-HT receptor(s) mediating contraction in the mouse aorta and the pathways these receptors are coupled with to mediate contraction. We hypothesized that a 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor agonist 伪-methyl-5-HT, and partial 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor agonist (卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (卤-DOI) caused the most potent and efficacious contraction. The 5-HT&lt;sub&gt;1E/1F&lt;/sub&gt; receptor agonist BRL 54443 also induced contraction (鈭抣og EC&lt;sub&gt;50&lt;/sub&gt; = 6.52); however, the 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor of the rat and the data generated in our experiments (鈭抣og EC&lt;sub&gt;50&lt;/sub&gt; and p&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;B&lt;/sub&gt; values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenyl&lt;i&gt;N&lt;/i&gt;,&lt;i&gt;N&lt;/i&gt;-diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT&lt;sub&gt;2A&lt;/sub&gt; receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases.&lt;/p&gt;" /> <meta name="citation_journal_title" content="Journal of Pharmacology and Experimental Therapeutics" /> <meta name="citation_publisher" content="American Society for Pharmacology and Experimental Therapeutics" /> <meta name="citation_publication_date" content="2001/04/01" /> <meta name="citation_mjid" content="jpet;297/1/88" /> <meta name="citation_id" content="297/1/88" /> <meta name="citation_public_url" content="https://jpet.aspetjournals.org/content/297/1/88" /> <meta name="citation_abstract_html_url" content="https://jpet.aspetjournals.org/content/297/1/88.abstract" /> <meta name="citation_full_html_url" content="https://jpet.aspetjournals.org/content/297/1/88.full" /> <meta name="citation_pdf_url" content="https://jpet.aspetjournals.org/content/jpet/297/1/88.full.pdf" /> <meta name="citation_issn" content="0022-3565" /> <meta name="citation_issn" content="1521-0103" /> <meta name="citation_journal_abbrev" content="J Pharmacol Exp Ther" /> <meta name="citation_pmid" content="11259531" /> <meta name="citation_volume" content="297" /> <meta name="citation_issue" content="1" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="CARDIOVASCULAR" /> <meta name="citation_firstpage" content="88" /> <meta name="citation_lastpage" content="95" /> <meta name="citation_author" content="C. 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Zwingelstein;citation_author=AJ. Sleight;citation_title=Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells.;citation_pages=713-720;citation_volume=36;citation_year=1996" /> <meta name="citation_reference" content="citation_journal_title=Neuropharmacology;citation_journal_abbrev=Neuropharmacology;citation_author=DW. Bonhaus;citation_author=KK. Weinhardt;citation_author=M. Taylor;citation_author=A. DeSouza;citation_author=PM. McNeeley;citation_author=K. Szczepanski;citation_author=DJ. Fontana;citation_author=J. Trinh;citation_author=CL. Rocha;citation_author=MW. Dawson;citation_title=RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist.;citation_pages=621-629;citation_volume=36;citation_year=1997;citation_issue=4-5;citation_pmid=9225287;citation_doi=10.1016/S0028-3908(97)00049-X" /> <meta name="citation_reference" content="citation_journal_title=British journal of pharmacology;citation_journal_abbrev=Br J Pharmacol;citation_author=AM. Brown;citation_author=K. Avenell;citation_author=TJ. Young;citation_author=M. Ho;citation_author=RA. Porter;citation_author=M. Vimal;citation_title=BRL 54443, a potent agonist with selectivity for the human cloned 5-ht1E and 5-ht1F receptors.;citation_pages=P233;citation_volume=123;citation_year=1998" /> <meta name="citation_reference" content="citation_journal_title=Journal of Pharmacology and Experimental Therapeutics;citation_journal_abbrev=J. Pharmacol. Exp. Ther.;citation_author=ML. Cohen;citation_author=RW. Fuller;citation_author=KS. 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Watts;citation_title=Integration of Mitogen-Activated Protein Kinase Kinase Activation in Vascular 5-Hydroxytryptamine2A Receptor Signal Transduction;citation_pages=346-355;citation_volume=284;citation_year=1997;citation_issue=1;citation_issn=0022-3565;citation_pmid=9435197" /> <meta name="citation_reference" content="citation_title=The Peripheral Actions of 5-Hydroxytryptamine.;citation_author=JA. Fozard;citation_year=1989" /> <meta name="citation_reference" content="citation_title=The Peripheral Actions of 5-hydroxytryptamine;citation_title=5-hydroxytryptamine receptors and effector coupling mechanisms in peripheral tissues;citation_author=D. Hoyer;citation_pages=72-95;citation_year=1989" /> <meta name="citation_reference" content="citation_journal_title=Pharmacological Reviews;citation_journal_abbrev=Pharmacol. Rev.;citation_author=D. Hoyer;citation_author=DE. Clark;citation_author=JR. Fozard;citation_author=PR. Hartig;citation_author=GR. Martin;citation_author=EJ. Mylecerane;citation_author=PR. Saxena;citation_author=PPA. Humphrey;citation_title=International Union of Pharmacology classification of receptors for 5- hydroxytryptamine (Serotonin);citation_pages=157-203;citation_volume=46;citation_year=1994;citation_issue=2;citation_issn=0031-6997;citation_pmid=7938165" /> <meta name="citation_reference" content="citation_journal_title=Am J Physiol;citation_author=DD. McGregor;citation_author=FH. Smirk;citation_title=Vascular responses to 5-hydroxytryptamine in genetic and renal hypertensive rats.;citation_pages=687-690;citation_volume=219;citation_year=1970" /> <meta name="citation_reference" content="citation_journal_title=Journal of Pharmacology and Experimental Therapeutics;citation_journal_abbrev=J. Pharmacol. Exp. Ther.;citation_author=T. Nakaki;citation_author=BL. Roth;citation_author=DM. Chaung;citation_author=E. Costa;citation_title=Phasic and tonic components in 5-HT2 receptor-mediated rat aorta contraction: participation of Ca++ channels and phospholipase C;citation_pages=442-446;citation_volume=234;citation_year=1985;citation_issue=2;citation_issn=0022-3565;citation_pmid=2410594" /> <meta name="citation_reference" content="citation_journal_title=Journal of Pharmacology and Experimental Therapeutics;citation_journal_abbrev=J. Pharmacol. Exp. Ther.;citation_author=BL. Roth;citation_author=T. Nakaki;citation_author=DM. Chaung;citation_author=E. Costa;citation_title=5-Hydroxytryptamine2 receptors coupled to phospholipase C in rat aorta: modulation of phosphoinositide turnover by phorbol ester;citation_pages=480-485;citation_volume=238;citation_year=1986;citation_issue=2;citation_issn=0022-3565;citation_pmid=3016238" /> <meta name="citation_reference" content="citation_journal_title=PNAS;citation_journal_abbrev=Proc. Natl. Acad. Sci. USA;citation_author=M. Ruat;citation_author=E. Traiffort;citation_author=R. Leurs;citation_author=J. Tardivel-Lacombe;citation_author=J. Diaz;citation_author=JM. Arrang;citation_author=JC. Schwartz;citation_title=Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation.;citation_pages=8547-8551;citation_volume=90;citation_year=1993;citation_issue=18;citation_issn=0027-8424;citation_pmid=8397408;citation_doi=10.1073/pnas.90.18.8547" /> <meta name="citation_reference" content="citation_journal_title=Lab Animal Sci;citation_author=G. Schlager;citation_author=J. Sides;citation_title=Characterization of hypertensive and hypotensive inbred strains of mice.;citation_pages=288-292;citation_volume=47;citation_year=1997" /> <meta name="citation_reference" content="citation_journal_title=Journal of Biological Chemistry;citation_journal_abbrev=J Biol Chem;citation_author=Y. Shen;citation_author=FJ. Monsma;citation_author=MA. Metcalf;citation_author=PA. Jose;citation_author=MW. Hamblin;citation_author=DR. Sibley;citation_title=Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype;citation_pages=18200-18204;citation_volume=268;citation_year=1993;citation_issue=24;citation_issn=0021-9258;citation_pmid=8394362" /> <meta name="citation_reference" content="citation_journal_title=British journal of pharmacology;citation_journal_abbrev=Br J Pharmacol;citation_author=JA. Terron;citation_title=The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype;citation_pages=1421-1428;citation_volume=118;citation_year=1996;citation_issue=6;citation_pmid=8832067" /> <meta name="citation_reference" content="citation_journal_title=British journal of pharmacology;citation_journal_abbrev=Br J Pharmacol;citation_author=ZP. To;citation_author=DW. Bonhaus;citation_author=RM. Eglen;citation_author=LB. Jakeman;citation_title=Characterization and distribution of putative 5-ht7 receptors in guinea- pig brain;citation_pages=107-116;citation_volume=115;citation_year=1995;citation_issue=1;citation_pmid=7647964" /> <meta name="citation_reference" content="citation_journal_title=American Journal of Physiology - Heart and Circulatory Physiology;citation_journal_abbrev=Am. J. Physiol. Heart Circ. Physiol.;citation_author=MB. Turla;citation_author=RC. Webb;citation_title=Augmented phosphoinositide metabolism in aortas from genetically hypertensive rats;citation_pages=H173-H178;citation_volume=258;citation_year=1990;citation_issue=1;citation_issn=0363-6135;citation_pmid=2154130" /> <meta name="citation_reference" content="citation_journal_title=Molecular Pharmacology;citation_journal_abbrev=Mol. Pharmacol.;citation_author=D. Wainscott;citation_author=ML. Cohen;citation_author=KW. Schenck;citation_author=JE. Audia;citation_author=JS. Nissen;citation_author=M. Baez;citation_author=JD. Kursar;citation_author=VL. Lucaites;citation_author=DL. Nelson;citation_title=Pharmacological characteristics of the newly cloned rat 5- hydroxytryptamine2F receptor;citation_pages=419-426;citation_volume=43;citation_year=1993;citation_issue=3;citation_issn=0026-895X;citation_pmid=8450835" /> <meta name="citation_reference" content="citation_journal_title=Journal of Pharmacology and Experimental Therapeutics;citation_journal_abbrev=J. Pharmacol. Exp. Ther.;citation_author=DB. Wainscott;citation_author=VL. Lucaites;citation_author=JD. Kursar;citation_author=M. Baez;citation_author=DL. Nelson;citation_title=Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences;citation_pages=720-727;citation_volume=276;citation_year=1996;citation_issue=2;citation_issn=0022-3565;citation_pmid=8632342" /> <meta name="citation_reference" content="citation_journal_title=Journal of hypertension;citation_journal_abbrev=J Hypertens;citation_author=SW. 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Schechter;citation_author=M. Macchi;citation_author=PR. Hartig;citation_author=TA. Branchek;citation_author=RL. Weinshank;citation_title=Human gene S31 encodes the pharmacologically defined serotonin 5- hydroxytryptamine1E receptor;citation_pages=180-185;citation_volume=42;citation_year=1992;citation_issue=2;citation_issn=0026-895X;citation_pmid=1513320" /> <meta name="twitter:title" content="Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://jpet.aspetjournals.org/sites/default/files/highwire/jpet/297/1.cover.gif" /> <meta name="twitter:description" content="The purpose of this study was to characterize pharmacologically the 5-HT receptor(s) mediating contraction in the mouse aorta and the pathways these receptors are coupled with to mediate contraction. We hypothesized that a 5-HT2A receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT2A receptor agonist 伪-methyl-5-HT, and partial 5-HT2A receptor agonist (卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (卤-DOI) caused the most potent and efficacious contraction. The 5-HT1E/1F receptor agonist BRL 54443 also induced contraction (鈭抣og EC50 = 6.52); however, the 5-HT2A receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT2A receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT2A receptor of the rat and the data generated in our experiments (鈭抣og EC50 and p K B values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenyl N , N -diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT2A receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases." /> <meta name="og-title" property="og:title" content="Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic Aorta and Signal Pathway Coupling" /> <meta name="og-url" property="og:url" content="https://jpet.aspetjournals.org/content/297/1/88" /> <meta name="og-site-name" property="og:site_name" content="Journal of Pharmacology and Experimental Therapeutics" /> <meta name="og-description" property="og:description" content="The purpose of this study was to characterize pharmacologically the 5-HT receptor(s) mediating contraction in the mouse aorta and the pathways these receptors are coupled with to mediate contraction. We hypothesized that a 5-HT2A receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT2A receptor agonist 伪-methyl-5-HT, and partial 5-HT2A receptor agonist (卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (卤-DOI) caused the most potent and efficacious contraction. The 5-HT1E/1F receptor agonist BRL 54443 also induced contraction (鈭抣og EC50 = 6.52); however, the 5-HT2A receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT2A receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT2A receptor of the rat and the data generated in our experiments (鈭抣og EC50 and p K B values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenyl N , N -diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT2A receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://jpet.aspetjournals.org/sites/default/files/highwire/jpet/297/1.cover.gif" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/297/1/88.ppt" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/297/1/88.full.txt" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/297/1/88.full.pdf" /> <link rel="canonical" href="https://jpet.aspetjournals.org/content/297/1/88" /> <link rel="shortcut icon" href="https://jpet.aspetjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <title>Characterization of the Serotonin Receptor Mediating Contraction in the Mouse Thoracic 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M. McKune</span> and <span class="highwire-citation-author" data-delta="1">S. W. Watts</span></span></div></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Journal of Pharmacology and Experimental Therapeutics </span><span class="highwire-cite-metadata-date highwire-cite-metadata">April 2001, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">297 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">88-95; </span></div> </div> <div id="hw-article-author-popups-top-node-38288--61717218793" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">C. M. 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We hypothesized that a 5-HT<sub>2A</sub> receptor, as in the rat, mediates contraction by activating L-type calcium channels, phospholipase C (PLC), and tyrosine kinase(s). Endothelium-denuded aortic strips were placed in a tissue bath for measurement of isometric contractile force. 5-HT, the 5-HT<sub>2A</sub> receptor agonist 伪-methyl-5-HT, and partial 5-HT<sub>2A</sub> receptor agonist (卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (卤-DOI) caused the most potent and efficacious contraction. The 5-HT<sub>1E/1F</sub> receptor agonist BRL 54443 also induced contraction (鈭抣og EC<sub>50</sub> = 6.52); however, the 5-HT<sub>2A</sub> receptor antagonist ketanserin antagonized this contraction. Our hypothesis was further supported by the finding that antagonists with affinity for the 5-HT<sub>2A</sub> receptor, ketanserin, 1-(1-naphthyl)piperazine, spiperone, and LY53857, reduced 5-HT-induced contraction. A correlation of 0.927 was found between literature-derived compound binding affinities for the agonists and antagonists at the 5-HT<sub>2A</sub> receptor of the rat and the data generated in our experiments (鈭抣og EC<sub>50</sub> and p<em>K</em><sub>B</sub> values). The L-type calcium channel blockers nifedipine and nitrendipine, PLC inhibitor 2-nitro-4-carboxyphenyl<em>N</em>,<em>N</em>-diphenylcarbamate, and tyrosine kinase inhibitors genistein and PD 098,059 all shifted and/or reduced maximum contraction to 5-HT. We conclude that contraction to 5-HT in the mouse aorta is mediated primarily by a 5-HT<sub>2A</sub> receptor and is coupled to L-type calcium channels, PLC, and tyrosine kinases.</p> </div><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn-corresp" id="fn-1"> <p id="p-1"><strong>Send reprint requests to:</strong> Carolyn McKune/Dr. Stephanie W. Watts, Department of Pharmacology and Toxicology, B445 Life Sciences Bldg., Michigan State University, East Lansing, MI 48824-1317. E-mail:<span class="em-link"><span class="em-addr">wattss{at}msu.edu</span></span></p> </li><li class="fn" id="fn-7"> <p id="p-50">The American Heart Association (Michigan Affiliate), as well as the College of Veterinary Medicine at Michigan State University, and National Institutes of Health HL 58489 generously funded part of this project.</p> </li><li class="glossary" id="glossary-1">Abbreviations:<dl id="def-list-1"><dt id="def-item-1">5-HT<span class="def-item-dt-sep"></span></dt><dd><span class="def">5-hydroxytryptamine</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-2">伪-methyl-5-HT<span class="def-item-dt-sep"></span></dt><dd><span class="def">伪-methyl serotonin maleate</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-3">PLC<span class="def-item-dt-sep"></span></dt><dd><span class="def">phospholipase C</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-4">PE<span class="def-item-dt-sep"></span></dt><dd><span class="def">phenylephrine</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-5"><em>m</em>-CPP<span class="def-item-dt-sep"></span></dt><dd><span class="def">1-(3-chlorophenyl)piperazine</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-6">5-CT<span class="def-item-dt-sep"></span></dt><dd><span class="def">5-carboxamidotryptamine maleate</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-7">dipropyl-5-CT<span class="def-item-dt-sep"></span></dt><dd><span class="def"><em>N</em>,<em>N</em>-dipropyl-5-carboxamidotryptamine maleate</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-8">PAPP<span class="def-item-dt-sep"></span></dt><dd><span class="def"><em>p</em>-aminophenylethyl-<em>m</em>-trifluoromethylphenyl piperazine</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-9">8-OH-DPAT<span class="def-item-dt-sep"></span></dt><dd><span class="def">(卤)-8-hydroxy-2-(di-<em>N</em>-propylamino)tetralin hydrobromide</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-10">DOI<span class="def-item-dt-sep"></span></dt><dd><span class="def">(卤)-2,5-dimethoxy-4-iodoamphetamine hydrochloride</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-11">2-Me-5-HT<span class="def-item-dt-sep"></span></dt><dd><span class="def">2-methyl-5-hydroxytryptamine maleate</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-12"><em>m</em>-CPBG<span class="def-item-dt-sep"></span></dt><dd><span class="def">1-(<em>m</em>-chlorophenyl)-biguanide hydrochloride</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-13">MAO<span class="def-item-dt-sep"></span></dt><dd><span class="def">monoamine oxidase</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-14">DMSO<span class="def-item-dt-sep"></span></dt><dd><span class="def">dimethyl sulfoxide</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-15">1-NP<span class="def-item-dt-sep"></span></dt><dd><span class="def">1-(1-naphthyl)piperazine hydrochloride</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-16">ICS 205-930<span class="def-item-dt-sep"></span></dt><dd><span class="def">3-tropanyl-indole-3-carboxylate hydrochloride</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-17">NCDC<span class="def-item-dt-sep"></span></dt><dd><span class="def">2-nitro-4-carboxyphenyl<em>N</em>,<em>N</em>-diphenylcarbamate</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-18">MAPKK<span class="def-item-dt-sep"></span></dt><dd><span class="def">mitogen-activated protein kinase kinase</span><span class="def-item-dd-sep"></span></dd><dt id="def-item-19">E<span class="def-item-dt-sep"></span></dt><dd><span class="def">efficacy</span></dd></dl></li><li class="history" id="history-1"><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2000-07-21"><span class="received-label">Received </span>July 21, 2000.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2000-12-07"><span class="accepted-label">Accepted </span>December 7, 2000.</li></ul></li></ul></div><ul><li class="copyright-statement" id="copyright-statement-1">The American Society for Pharmacology and Experimental Therapeutics</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="https://jpet.aspetjournals.org/content/297/1/88.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-jpet-challenge" > <div class="pane-content"> <div class="panel-display highwire-1col-stacked-layout" id="mini-panel-jnl_jpet_challenge"> <div class="panel-row-wrapper panel-row-first clearfix"> <div class="top-wrapper"> <div class="panel-panel 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