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In mice, NK<jats:sub>1<\/jats:sub> tachykinin receptors are involved in SP\u2010induced itch\u2010associated responses, scratching, and mast cells do not play a critical role. The present study was conducted to elucidate the role of nitric oxide (NO) on SP\u2010induced scratching in mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An intradermal injection of SP (100 nmol site<jats:sup>\u22121<\/jats:sup>) elicited scratching in mice, and it was suppressed by an intravenous injection of the NO synthase (NOS) inhibitor <jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine methyl ester (<jats:sc>L<\/jats:sc>\u2010NAME), but not by its inactive enantiomer <jats:sc>D<\/jats:sc>\u2010NAME. Intradermal injections of <jats:sc>L<\/jats:sc>\u2010NAME (100 nmol site<jats:sup>\u22121<\/jats:sup>), another NOS inhibitor 7\u2010nitroindazole (10 nmol site<jats:sup>\u22121<\/jats:sup>) and the NO scavenger haemoglobin (0.01\u201310 nmol site<jats:sup>\u22121<\/jats:sup>) also inhibited SP\u2010induced scratching.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:sc>L<\/jats:sc>\u2010NAME (100 nmol site<jats:sup>\u22121<\/jats:sup>) did not affect scratching induced by an intradermal injection of 5\u2010hydroxytryptamine (100 nmol site<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Intradermal injections of <jats:sc>L<\/jats:sc>\u2010arginine (300 nmol site<jats:sup>\u22121<\/jats:sup>) and the NO donor (\u00b1)\u2010(E)\u20104\u2010ethyl\u20102\u2010[(E)\u2010hydroxyimino]\u20105\u2010nitro\u20103\u2010hexenamide (NOR3; 100 nmol site<jats:sup>\u22121<\/jats:sup>) increased scratching induced by SP. Intradermal injections of <jats:sc>L<\/jats:sc>\u2010arginine (1\u20131000 nmol site<jats:sup>\u22121<\/jats:sup>) or NOR3 (1\u2013100 nmol site<jats:sup>\u22121<\/jats:sup>) alone were without effects on scratching.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Intradermal injections of SP (10\u2013100 nmol site<jats:sup>\u22121<\/jats:sup>) increased the intradermal concentration of NO in a dose\u2010dependent manner in mice. An increase in NO levels induced by SP was inhibited by <jats:sc>L<\/jats:sc>\u2010NAME and the NK<jats:sub>1<\/jats:sub> tachykinin receptor antagonist L\u2010668,169, but not by the NK<jats:sub>2<\/jats:sub> tachykinin receptor antagonist L\u2010659,877.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SP (1\u201310 \u03bc<jats:sc>M<\/jats:sc>) elicited NO production in cultured human keratinocytes and the SP\u2010induced NO production was inhibited by <jats:sc>L<\/jats:sc>\u2010NAME and L\u2010668,169.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that intradermal SP increases NO in the skin, possibly through the action on NK<jats:sub>1<\/jats:sub> tachykinin receptors on the epidermal keratinocytes and that NO enhances SP\u2010induced itch\u2010associated responses.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>138<\/jats:bold>, 202\u2013208. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705004\">10.1038\/sj.bjp.0705004<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705004","type":"journal-article","created":{"date-parts":[[2003,1,9]],"date-time":"2003-01-09T19:22:37Z","timestamp":1042140157000},"page":"202-208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Nitric oxide enhances substance P\u2010induced itch\u2010associated responses in mice"],"prefix":"10.1111","volume":"138","author":[{"given":"Tsugunobu","family":"Andoh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Kuraishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01585.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01114-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00440-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00637-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01617-X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(95)00244-M"},{"key":"e_1_2_8_8_1","first-page":"1140","article-title":"Substance P induction of itch\u2010associated response mediated by cutaneous NK1 tachykinin receptors in mice","volume":"286","author":"ANDOH T.","year":"1998","journal-title":"J. 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