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NK 1 ‐receptors mediate the proliferative response of human fibroblasts to tachykinins
Author(s) -
Ziche Marina,
Morbidelli Lucia,
Pacini Marco,
Dolara Piero,
Maggi Carlo Alberto
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12043.x
Subject(s) - substance p , neurokinin b , neurokinin a , tachykinin receptor , receptor , medicine , endocrinology , agonist , cell growth , fibroblast , tachykinin receptor 1 , biology , chemistry , cell culture , neuropeptide , biochemistry , genetics
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‐Ala 4 , Sar 9 , Met(O 2 ) 11 ]‐SP(4–11), [β‐Ala 8 ]‐NKA(4–10) and [MePhe 7 ]‐NKB selective for NK 1 ‐, NK 2 ‐ and NK 3 ‐receptors respectively. Cell proliferation was measured by percentage increase in cell number and by [ 3 H]‐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 NK 1 ‐receptor agonist produced a dose‐dependent increase in cell proliferation as judged by total cell number and [ 3 H]‐thymidine uptake. No significant effect was observed with NK 2 ‐ and NK 3 ‐receptor agonists. 5 These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK 1 ‐receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.