Melatonin differentially modulates the expression and function of the hMT1 and hMT2 melatonin receptors upon prolonged withdrawal.
Melatonin differentially modulates the expression and function of the hMT1 and hMT2 melatonin receptors upon prolonged withdrawal.
复制标题
长期戒断后，褪黑素会差异性地调节 hMT1 和 hMT2 褪黑素受体的表达和功能。
DOI：
10.1016/s0006-2952(02)01627-1
复制
发表时间：
2003
影响因子：
5.8
通讯作者：
Dubocovich,MargaritaL
中科院分区：
文献类型：
--
作者：
Masana,MonicaI;Witt-Enderby,PaulaA;Dubocovich,MargaritaL
褪黑激素的合成和释放遵循昼夜节律，并在夜间达到其最高血液水平。它将黑暗信号传递到参与调节昼夜节律和季节性节律的目标组织。在这里，我们报告的表达人类褪黑激素受体1型和2型（hMT 1和hMT 2，分别）在中国仓鼠卵巢（CHO）细胞暴露于褪黑激素治疗模拟的幅度（400 pM）和持续时间（8小时）的夜间褪黑激素峰值和撤药后。CHO-MT 1细胞暴露于褪黑激素（400 pM）0.5、1、2、4和8小时显著增加2-[125 I]iodomelatonin（500 pM）与hMT 1褪黑激素受体的特异性结合。然而，相同的处理并不影响hMT 2褪黑激素受体的表达。撤褪黑激素后16小时2-[125 I]iodomelatonin（500 pM）特异性结合率（162± 29%，N=3，P<0.05）的增加与hMT 1褪黑激素受体mRNA的增加（231± 33%，N=4，P<0.05）平行。这种效应是由于hMT 1受体总数增加[Bmax 833 ± 97 fmol/mg蛋白（N=3），对照; 1449± 41 fmol/mg蛋白（N=3），处理]，结合亲和力无变化。褪黑激素介导的MT 1褪黑激素受体表达的增加，在撤药后不介导通过启动子的载体中的激素的直接作用或mRNA降解的速率。总之，褪黑激素差异调节其自身受体的表达，这可能具有重要的意义，在体内暗信号的转导。
Melatonin is synthesized and released following a circadian rhythm and reaches its highest blood levels during the night. It relays signals of darkness to target tissues involved in regulating circadian and seasonal rhythms. Here, we report the expression of human melatonin receptors type 1 and 2 (hMT1and hMT2, respectively) in Chinese hamster ovary (CHO) cells following exposure to melatonin treatments mimicking the amplitude (400pM) and duration (8hr) of the nightly melatonin peak and upon withdrawal. Exposure of CHO-MT1cells to melatonin (400pM) for 0.5, 1, 2, 4, and 8hr significantly increased specific 2-[125I ]iodomelatonin (500pM) binding to hMT1melatonin receptors upon 16-hr withdrawal. However, the same treatment did not affect the expression of hMT2melatonin receptors. The increase in specific 2-[125I ]iodomelatonin (500pM) binding (162±29%, N=3, P<0.05) 16hr after melatonin withdrawal was parallel to increases in hMT1melatonin receptor mRNA (231±33%, N=4, P<0.05). This effect was due to an increase in the total number of hMT1receptors [Bmax833±97fmol/mg protein (N=3), control; 1449±41fmol/mg protein (N=3), treated], with no change in binding affinity. The melatonin-mediated increase in MT1melatonin receptor expression upon withdrawal was not mediated through either a direct effect of the hormone in the promoter’s vector or in the rate of mRNA degradation. In conclusion, melatonin differentially regulates the expression of its own receptors, which may have important implications in the transduction of dark signals in vivo.