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). Selecti ve antagonists for the NK, receptor ([D-Pro4, D-Trp7,9, Phe11]-SP(4-11 ), GR71251 a nd L 668,169) and the NK2 receptor (L 659,877) were teste d against Substance P (SP), against the selective NK1 receptor agonist [beta-Ala 4, Sar9, Met(02)11]-SP(4-11) and against basic Fibroblast G rowth Factor (bFGF). All the selective NK1 receptor antagonists, teste d 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 sele ctive NK1 receptor agonist. The selective NK2 receptor antagonist did not modify the proliferative response to the tachykinins used. The gro wth promoting effect of bFGF was not modified by any of the tachykinin antagonists tested. These results indicate that the newly developed r eceptor-selective tachykinin antagonists appear to be a useful tool to assess the biological effects of tachykinin in vitro on cultured isol ated cells.