We investigated the effects of substance P (SP) on nitric oxide (NO) syntha
se activity in macrophages by measuring the production of nitrite and the e
xpression of inducible NO synthase (iNOS) mRNA and protein. In LPS-activate
d macrophages, SP stimulated NO production in time and concentration depend
ent manners. These SP effects were blocked by a specific NX-l receptor anta
gonist. Furthermore, SP stimulation increased the levels of both iNOS mRNA
and iNOS protein. These results demonstrate that SP can increase LPS induce
d NO production in macrophages by augmenting the induction of iNOS expressi
on. We also examined the role of SP on acute-cold stress induced altered pr
oduction of NO by mouse peritoneal macrophages. SP enhanced the LPS-induced
macrophages NO production from stressed mice relative to the non-stressed
mice. These results suggest that SP may have an important modulatory role i
n production of NO by macrophages. (C) 1999 Elsevier Science B.V. All right
s reserved.