Functional activity of serotoninergic and melatoninergic systems expressed in the skin
Functional activity of serotoninergic and melatoninergic systems expressed in the skin
复制标题
DOI：
10.1002/jcp.10287
复制
发表时间：
2003-07-01
影响因子：
5.6
通讯作者：
Wortsman, J
中科院分区：
文献类型：
--
作者：
Slominski, A;Pisarchik, A;Wortsman, J
我们测试了编码皮肤5-羟色胺/褪黑素能系统受体的基因在整个人类皮肤以及正常和病理培养的皮肤细胞中的表达。对5羟色胺(5 HT)、褪黑素(MT)和褪黑素相关受体(MRR)的检测显示，几乎所有受试样本都表达5HT2b、5HT7和MT1基因。其他异构体的表达较少；5HT2C、MRR和MT2很少检测到。我们还发现了MT2、MRR和5HT2b的新异构体，并记录了5HT2C的RNA编辑过程。用5-羟色胺和褪黑素(10(-14)至10(-10)M)测试这些受体的功能活性显示，根据细胞类型和培养条件的不同，这些受体的作用不同。因此，5-羟色胺在没有生长因子的培养液中刺激黑素细胞的增殖，而在存在生长因子的情况下抑制细胞的生长。褪黑素既能抑制无血清培养的HaCaT角质形成细胞的凋亡，又能抑制含血清培养的角质形成细胞增殖。褪黑素还可以增加在无血清培养中培养的成纤维细胞的存活数量。N-乙酰-5-羟色胺(NAS)和5-甲氧基色胺(5-MTT)对黑素细胞的增殖无明显影响，但在10-10M的5-甲氧基色胺浓度较高时可抑制黑素细胞的增殖。因此，皮肤细胞是5-羟色胺/褪黑素能皮肤通路产物的真正靶点，其作用是调节细胞的增殖或活力。(C)2003年Wiley-Liss，Inc.
We tested the expression of genes coding receptors of a cutaneous serotoninergic/melatoninergic system in whole human skin and in normal and pathologic cultured skin cells. Evaluation of serotonin (5HT), melatonin (MT), and melatonin-related receptors (MRR) showed expression of the isoforms 5HT2B, 5HT7, and MT1 genes in almost all the tested samples. Expression of other isoforms was less prevalent; 5HT2C, MRR, and MT2 were rarely detected. We also found novel isoforms for MT2, MRR, and 5HT2B and documented the process of RNA editing for 5HT2C. Testing for functional activity of these receptors with serotonin and melatonin (10(-14) to 10(-10) M) showed variable effects depending on cell type and culture conditions. Thus, serotonin stimulated proliferation of melanocytes in medium deprived of growth factors, while inhibiting cell growth in the presence of growth factors. Melatonin inhibited both apoptosis of HaCaT keratinocytes incubated in serum-free media, and proliferation of cells cultured in medium supplemented with serum. Melatonin also increased the numbers of viable fibroblasts incubated in serum free medium. N-acetylserotonin (NAS) and 5 methoxytryptamine (5MTT) were generally without effect on cell proliferation, with the exception of an inhibition of melanocyte proliferation at the higher 5MTT concentration of 10-10 M. Thus, skin cells represent a true target for the products of the serotoninergic/melatoninergic cutaneous pathway with their actions modulating cell proliferation or viability. (C) 2003 Wiley-Liss, Inc.