Substance P augments nitric oxide production and gene expression in murinemacrophages

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.