{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:33:47Z","timestamp":1791110027414,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,11,2]],"date-time":"2005-11-02T00:00:00Z","timestamp":1130889600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>The neuropeptide substance P is known to be localized in nerve terminals in human skin and substance P\u2010induced vasodilatation is believed to be partially dependent on nitric oxide (NO) and H1 histamine receptor activation. Unlike other neuropeptides investigated in human skin, substance P\u2010induced vasodilatation has been shown to decline during continuous infusion, possibly suggestive of an internalization of neurokinin\u20101 (NK<jats:sub>1<\/jats:sub>) receptors, which are highly specific to substance P. However, questions remain regarding these mechanisms in human skin. Fifteen subjects participated in this series of studies designed to investigate the effect of consecutive infusions and possible mechanisms of substance P\u2010induced vasodilatation in human skin. Two concentrations of substance P (10 \u03bc<jats:sc>m<\/jats:sc>and 20 \u03bc<jats:sc>m<\/jats:sc>) were tested via intradermal microdialysis in two groups of subjects. Site 1 served as a control and received substance P only. Site 2 received substance P combined with 10 m<jats:sc>m l<\/jats:sc>\u2010NAME to inhibit NO synthase. Site 3 received substance P combined with 500 \u03bc<jats:sc>m<\/jats:sc>pyrilamine, an H1 receptor antagonist. Site 4 received substance P combined with 10 m<jats:sc>m l<\/jats:sc>\u2010NAME plus 500 \u03bc<jats:sc>m<\/jats:sc>pyrilamine. Red blood cell (RBC) flux was measured via laser\u2010Doppler flowmetry to provide an index of skin blood flow. Cutaneous vascular conductance was calculated as RBC flux\/mean arterial pressure and was normalized to maximal vasodilatation via 28 m<jats:sc>m<\/jats:sc>sodium nitroprusside. Substance P was perfused through each microdialysis fibre at a rate of 4 \u03bcl min<jats:sup>\u22121<\/jats:sup>for 15 min. The subsequent increase in skin blood flow was allowed to return to baseline (\u223c45\u201360 min) and a stable 5 min plateau was used as a new baseline (post\u2010infusion baseline). A second dose of substance P was then delivered to the skin and skin blood flow was monitored for 45\u201360 min. Substance P produced a dose\u2010dependent increase in skin blood flow with the concentrations of substance<jats:italic>P<\/jats:italic>tested, which was significantly attenuated in the presence of<jats:sc>l<\/jats:sc>\u2010NAME and the combination of<jats:sc>l<\/jats:sc>\u2010NAME plus pyrilamine. However, substance P\u2010induced vasodilatation was unaffected in the presence of pyrilamine. There was no significant difference between the<jats:sc>l<\/jats:sc>\u2010NAME\u2010only sites and the<jats:sc>l<\/jats:sc>\u2010NAME plus pyrilamine sites. Importantly, the second dose of substance P did not produce a significant increase in skin blood flow compared to the initial baseline or the post\u2010infusion baseline. These data suggest substance P\u2010induced vasodilatation delivered via microdialysis contains an NO component but does not contain an H1 receptor activation component at the doses tested. Additionally, these data provide evidence for NK<jats:sub>1<\/jats:sub>receptor desensitization as there was no observable increase in skin blood flow following a second administration of substance P. This may provide a useful model for studying the role of substance P in the control of skin blood flow in humans.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.095372","type":"journal-article","created":{"date-parts":[[2005,8,26]],"date-time":"2005-08-26T00:24:27Z","timestamp":1125015867000},"page":"1047-1056","source":"Crossref","is-referenced-by-count":37,"title":["Neurokinin\u20101 receptor desensitization to consecutive microdialysis infusions of substance P in human skin"],"prefix":"10.1113","volume":"568","author":[{"given":"Brett J.","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Tublitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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