{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:05:46Z","timestamp":1772885146888,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3968,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In the Fisher 344 rat, tachykinins have been shown to cause the release of 5\u2010hydroxytryptamine (5\u2010HT) from airway mast cells, which then causes direct smooth muscle activation as well as the release of acetylcholine from cholinergic nerves. The aim of the present study was to examine the modulatory effects of 5\u2010HT receptors on the neurokinin A (NKA)\u2010induced release of endogenous 5\u2010HT and airway smooth muscle contraction in the isolated Fisher 344 rat trachea.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The selective 5\u2010HT<jats:sub>2<\/jats:sub> receptor antagonist ketanserin (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) produced an almost complete inhibition of the contractions caused by NKA (<jats:italic>n<\/jats:italic>=4, P&lt;0.0001, two\u2010way ANOVA), and a significant rightward shift of the concentration\u2010response curve to 5\u2010HT (<jats:italic>n<\/jats:italic>=8, <jats:italic>P<\/jats:italic>&lt;0.001, two\u2010way ANOVA).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The partial agonist for 5\u2010HT<jats:sub>1A<\/jats:sub> receptors, 8\u2010OH\u2010DPAT (1\u2003\u03bc<jats:sc>M<\/jats:sc>), and the full agonist for 5\u2010HT<jats:sub>1<\/jats:sub> receptors, 5\u2010CT (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>), potentiated the submaximal contractions induced by the 5\u2010HT<jats:sub>2<\/jats:sub> receptor agonist \u03b1\u2010methyl\u20105\u2010HT (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) (<jats:italic>n<\/jats:italic>=4; <jats:italic>P<\/jats:italic>&lt;0.005 and <jats:italic>P<\/jats:italic>&lt;0.05, respectively). 8\u2010OH\u2010DPAT (1\u2003\u03bc<jats:sc>M<\/jats:sc>), as well as the 5\u2010HT<jats:sub>1A<\/jats:sub> receptor antagonists pMPPI, SDZ 216525 and NAN\u2010190 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc> each), caused significant inhibition of the tracheal contractions induced both by NKA (10\u2003\u2003n<jats:sc>M<\/jats:sc>\u20133\u2003\u2003\u03bc<jats:sc>M<\/jats:sc>) and 5\u2010HT (10\u2003n<jats:sc>M<\/jats:sc>\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>) (<jats:italic>n<\/jats:italic>=4\u201310). This suggests that activation of 5\u2010HT<jats:sub>1A<\/jats:sub> receptors potentiates the 5\u2010HT<jats:sub>2<\/jats:sub> receptor\u2010mediated contractions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SDZ 216525 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) significantly reduced the maximal contraction produced by 1\u2003\u03bc<jats:sc>M<\/jats:sc> NKA (<jats:italic>n<\/jats:italic>=10, <jats:italic>P<\/jats:italic>&lt;0.001), without affecting the release of endogenous 5\u2010HT. These data rule out the involvement of a 5\u2010HT<jats:sub>1A<\/jats:sub> receptor\u2010mediated positive feedback mechanism of the 5\u2010HT release from mast cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Even in the presence of atropine (1\u2003\u03bc<jats:sc>M<\/jats:sc>), 8\u2010OH\u2010DPAT (1\u2003\u03bc<jats:sc>M<\/jats:sc>) further reduced the maximal NKA\u2010induced contraction (<jats:italic>n<\/jats:italic>=4, <jats:italic>P<\/jats:italic>&lt;0.0001), while the contractions of the rat isolated trachea induced by electrical field stimulation and the concentration\u2010response curve to carbachol were unaffected by pMPPI (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>), SDZ 216525 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>), NAN\u2010190 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) and 8\u2010OH\u2010DPAT (1\u2003\u03bc<jats:sc>M<\/jats:sc>) (<jats:italic>n<\/jats:italic>=4\u20136). These data demonstrate that the 5\u2010HT<jats:sub>1A<\/jats:sub> receptor\u2010mediated potentiation of contractile responses is not due to non\u2010specific inhibition of airway smooth muscle contraction or to modulation of postganglionic nerve activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The selective 5\u2010HT<jats:sub>1B\/1D<\/jats:sub> receptor antagonist GR 127935, the selective 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist tropisetron and the selective 5\u2010HT<jats:sub>4<\/jats:sub> receptor antagonists SB 204070 and GR 113808 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc> each) had no effect on the concentration\u2010response curve for NKA (<jats:italic>n<\/jats:italic>=6\u201310), ruling out the involvement of 5\u2010HT<jats:sub>1B\/1D<\/jats:sub>, 5\u2010HT<jats:sub>3<\/jats:sub> and 5\u2010HT<jats:sub>4<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The \u03b1\u2010adrenoreceptor antagonist phentolamine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) had no effect on the 5\u2010HT\u2010induced contractions (<jats:italic>n<\/jats:italic>=4), ruling out the involvement of \u03b1\u2010adrenoreceptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, the tachykinin\u2010induced contraction of the F334 rat isolated trachea is mediated by the stimulation of 5\u2010HT<jats:sub>2<\/jats:sub> receptors. Activation of 5\u2010HT<jats:sub>1A<\/jats:sub> receptors located on airway smooth muscle potentiates the direct contractile effects of 5\u2010HT<jats:sub>2<\/jats:sub> receptor activation. The 5\u2010HT<jats:sub>1B\/1D<\/jats:sub>, 5\u2010HT<jats:sub>3<\/jats:sub> and 5\u2010HT<jats:sub>4<\/jats:sub> receptors are not involved in the NKA\u2010induced contraction of rat airways.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 1571\u20131578; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701771\">10.1038\/sj.bjp.0701771<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701771","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:27:23Z","timestamp":1106940443000},"page":"1571-1578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Modulation by 5\u2010HT<sub>1A<\/sub> receptors of the 5\u2010HT<sub>2<\/sub> receptor\u2010mediated tachykinin\u2010induced contraction of the rat trachea <i>in vitro<\/i>"],"prefix":"10.1111","volume":"123","author":[{"given":"P. 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