NK1‐receptors mediate the proliferative response of human fibroblasts to tachykinins

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Abstract
1 The effect of synthetic tachykinin selective receptor agonists was studied on the growth of cultured human skin fibroblasts (HF). 2 Human fibroblasts were grown in serum-free conditions in the presence of natural tachykinins (substance P and neurokinin A) and of three synthetic agonists, [β-Ala4, Sar9, Met(O2)11]-SP(4–11), [β-Ala8]-NKA(4–10) and [MePhe7]-NKB selective for NK1-, NK2- and NK3-receptors respectively. Cell proliferation was measured by percentage increase in cell number and by [3H]-thymidine uptake following 48 h exposure to agents compared to baseline condition. 3 Neurokinin A (NKA) and substance P (SP) significantly increased cell proliferation the threshold concentrations being 10−12 and 10−11 m, respectively. Addition of thiorphan to culture conditions enhanced the effect of SP but not of NKA. 4 The selective NK1-receptor agonist produced a dose-dependent increase in cell proliferation as judged by total cell number and [3H]-thymidine uptake. No significant effect was observed with NK2- and NK3-receptor agonists. 5 These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK1-receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.