NK1受体介导人类成纤维细胞对速激肽的增殖反应。

NK1-receptors mediate the proliferative response of human fibroblasts to tachykinins.

Ziche M, Morbidelli L, Pacini M, Dolara P, Maggi C A

Department of Preclinical and Clinical Pharmacology, Mario Aiazzi Mancini, University of Florence, Italy.

Br J Pharmacol. 1990 May;100(1):11-4. doi: 10.1111/j.1476-5381.1990.tb12043.x.

Abstract

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, [beta-Ala4, Sar9, Met(O2)11]-SP(4-11), [beta-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.

摘要

研究了合成速激肽选择性受体激动剂对培养的人皮肤成纤维细胞（HF）生长的影响。2. 人成纤维细胞在无血清条件下，于天然速激肽（P物质和神经激肽A）以及三种分别对NK1、NK2和NK3受体具有选择性的合成激动剂[β-丙氨酸4，Sar9，Met（O2）11]-SP（4-11）、[β-丙氨酸8]-NKA（4-10）和[MePhe7]-NKB存在的情况下生长。与基线条件相比，在接触试剂48小时后，通过细胞数量的百分比增加和[3H]胸腺嘧啶核苷摄取来测量细胞增殖。3. 神经激肽A（NKA）和P物质（SP）显著增加细胞增殖，阈值浓度分别为10^(-12)和10^(-11)M。在培养条件中添加硫磷酰胺增强了SP的作用，但未增强NKA的作用。4. 选择性NK1受体激动剂通过总细胞数量和[3H]胸腺嘧啶核苷摄取判断，使细胞增殖呈剂量依赖性增加。NK2和NK3受体激动剂未观察到显著作用。5. 这些数据表明，SP对成纤维细胞增殖的作用是通过与NK1受体类型相互作用介导的，局部代谢可干扰SP对细胞增殖这一作用的充分表达。