Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis

Three types of tachykinin receptors, namely NK₁, NK₂ and NK₃, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones. This study evaluated the effects of mammalian tachykinins and selective tachykinin agonists and antagonists on human monocytes isolated from healthy donors: SP, NKA and NKB all evoked a dose-dependent superoxide anion (O₂^-) production and the NK₂ selective agonist [β-Ala⁸]-NKA(4-10) induced a full response. The NK₃ selective agonist senktide was inactive, while the NK₁ selective agonists septide and [Sar⁹Met(O₂)¹¹]SP displayed some effects. These results indicate that NK₂ and also some NK₁ receptors are present in monocytes isolated from healthy donors. The role of tachykinin receptor activation in rheumatoid arthritis was also investigated, by measuring O₂^- production and TNF-α mRNA expression in monocytes isolated from rheumatoid patients. Tachykinins enhanced the expression of this cytokine in both control and rheumatoid monocytes and NK₂ receptor stimulation was shown to trigger an enhanced respiratory burst in monocytes from rheumatoid patients. In conclusion, these results indicate that NK₂ and NK₁ receptors are present on human monocytes, the former being preferentially involved in rheumatoid arthritis.