Effect of selective tachykinin receptor antagonists on the growth of human skin fibroblasts.

The effect of synthetic selective tachykinin receptor antagonists was studied on the growth of cultured human skin fibroblasts (HF). Selective antagonists for the NK1 receptor ([D-Pro4, D-Trp7,9,Phe11]-SP(4-11), GR71251 and L 668,169) and the NK2 receptor (L 659,877) were tested against Substance P (SP), against the selective NK1 receptor agonist [beta-Ala4,Sar9, Met(O2)11]-SP(4-11) and against basic Fibroblast Growth Factor (bFGF). All the selective NK1 receptor antagonists, tested at the concentration of 10(-5)M, induced a significant displacement to the right of the dose-response curves induced by SP and by the selective NK1 receptor agonist. The selective NK2 receptor antagonist did not modify the proliferative response to the tachykinins used. The growth promoting effect of bFGF was not modified by any of the tachykinin antagonists tested. These results indicate that the newly developed receptor-selective tachykinin antagonists appear to be a useful tool to assess the biological effects of tachykinin in vitro on cultured isolated cells.