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100\u2003\u03bc<jats:sc>M<\/jats:sc>) had no significant effect on the response induced by 1\u2003\u03bc<jats:sc>M<\/jats:sc> substance P.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The enhancement of constriction rate induced by 1\u2003\u03bc<jats:sc>M<\/jats:sc> substance P was prevented by the cyclo\u2010oxygenase inhibitor, indomethacin (3\u2003\u03bc<jats:sc>M<\/jats:sc>), the thromboxane A<jats:sub>2<\/jats:sub> synthase inhibitor, imidazole (50\u2003\u03bc<jats:sc>M<\/jats:sc>), and the thromboxane A<jats:sub>2<\/jats:sub> receptor antagonist, SQ29548 (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The stable analogue of thromboxane A<jats:sub>2<\/jats:sub>, U46619 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) significantly increased the constriction rate of lymphangions with or without endothelium, an effect which was prevented by SQ29548 (0.3\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Treatment with pertussis toxin (PTx; 100\u2003ng ml<jats:sup>\u22121<\/jats:sup>) completely abolished the response to 1\u2003\u03bc<jats:sc>M<\/jats:sc> substance P without inhibiting either the perfusion\u2010induced constriction or the U46619\u2010induced enhancement of constriction rate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Application of the phospholipase A<jats:sub>2<\/jats:sub> inhibitor, antiflammin\u20101 (1\u2003n<jats:sc>M<\/jats:sc>) prevented the enhancement of lymphatic pumping induced by substance P (1\u2003\u03bc<jats:sc>M<\/jats:sc>), without inhibiting the response to either U46619 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) or acetylcholine (10\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data support the hypothesis that the substance P\u2010induced increase in pumping rate is mediated via the endothelium through NK<jats:sub>1<\/jats:sub> receptors coupled by a PTx sensitive G\u2010protein to phospholipase A<jats:sub>2<\/jats:sub> and resulting in generation of the arachidonic acid metabolite, thromboxane A<jats:sub>2<\/jats:sub>, this serving as the diffusible activator.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>121<\/jats:bold>, 1589\u20131596; 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