Uchida-Oka N, Sugimoto M
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
Pigment Cell Res. 2001 Oct;14(5):356-61. doi: 10.1034/j.1600-0749.2001.140507.x.
The density of skin melanophores in many teleost fish decreases during long-term adaptation to a white background. Using the medaka, Oryzias latipes, we previously reported that apoptosis is responsible for the decrease in melanophores, and that a sympathetic neurotransmitter, norepinephrine (NE), induces their apoptosis in skin tissue cultures. In this study, we show that NE-induced apoptosis of melanophores is mediated by the activation of alpha2-adrenoceptors. Clonidine, an alpha2-adrenoceptor agonist, induced apoptotic melanophore death in skin organ culture, while phenylephrine, an alpha1-adrenoceptor agonist, had no effect. NE-induced apoptosis was diminished by an alpha2-adrenoceptor antagonist, yohimbine, but an alpha1-adrenoceptor antagonist, prazosin, did not abrogate the effect of NE. Furthermore, forskolin inhibited NE-induced apoptosis, while an inhibitor of PKA, H-89, mimicked the effect of NE. These results suggest that NE induces apoptosis in melanophores by attenuating cAMP-PKA signaling via alpha2-adrenoceptors.
在许多硬骨鱼长期适应白色背景的过程中，其皮肤黑素细胞的密度会降低。我们之前利用青鳉（Oryzias latipes）报道过，黑素细胞数量的减少是由细胞凋亡引起的，并且一种交感神经递质去甲肾上腺素（NE）在皮肤组织培养中可诱导黑素细胞凋亡。在本研究中，我们发现NE诱导的黑素细胞凋亡是由α2 -肾上腺素能受体的激活介导的。α2 -肾上腺素能受体激动剂可乐定在皮肤器官培养中可诱导黑素细胞发生凋亡性死亡，而α1 -肾上腺素能受体激动剂去氧肾上腺素则无此作用。α2 -肾上腺素能受体拮抗剂育亨宾可减少NE诱导的凋亡，但α1 -肾上腺素能受体拮抗剂哌唑嗪并不能消除NE的作用。此外，福斯可林可抑制NE诱导的凋亡，而蛋白激酶A抑制剂H - 89则模拟了NE的作用。这些结果表明，NE通过α2 -肾上腺素能受体减弱cAMP - PKA信号传导，从而诱导黑素细胞凋亡。
