Ziegler Michael G, Bao Xuping, Kennedy Brian P, Joyner Alex, Enns Robert
University of California San Diego Medical Center, San Diego, California 92103, USA.
Ann N Y Acad Sci. 2002 Oct;971:76-82. doi: 10.1111/j.1749-6632.2002.tb04437.x.
Phenylethanolamine N-methyltransferase (PNMT) methylates norepinephrine (NE) to form epinephrine (E). It is present in a high concentration in the adrenal medula but occurs in many other tissues throughout the body. In the brain stem and retina PNMT is present in specific neurons. Cardiac PNMT develops early in the fetal heart and is found in relatively high levels in the adult left atrium. Intrinsic cardiac adrenergic cells are distributed throughout the adult myocardium and contain all the enzymes necessary for E synthesis. The PNMT gene promoter region contains a glucocorticoid response element; however, the initial development of brain and cardiac fetal PNMT is glucocorticoid independent. Rat fetal heart PNMT peaks at embryonic day 11 and becomes sensitive to glucocorticoid induction by day 12. PNMT-containing cells are concentrated in the atrioventricular canal and interventricular septum during cardiac development, areas important in the development of the cardiac conduction system. In the adult rat, cardiac PNMT is inducible by glucocorticoids and synthesizes E. Glucocorticoids are essential for development of the high levels of PNMT in the adrenal, but are less important outside the adrenal. The PNMT gene contains 3 exons and 2 introns. Adrenal PNMT mRNA exists as a single type, but in the heart PNMT mRNA is present as both an intronless and an intron-containing type. In some cardiac tissues, glucocorticoids decrease levels of intron-containing PNMT mRNA and increase intronless PNMT mRNA and PNMT activity. Studies in adrenalectomized animals suggest that extraadrenal PNMT increases blood pressure, blood glucose, and lymphocyte cytokine production. PNMT may also play a role in the regulation of fetal heart rate prior to development of the adrenal medulla.
苯乙醇胺N-甲基转移酶（PNMT）将去甲肾上腺素（NE）甲基化形成肾上腺素（E）。它在肾上腺髓质中浓度很高，但在全身许多其他组织中也有存在。在脑干和视网膜中，PNMT存在于特定神经元中。心脏PNMT在胎儿心脏早期发育时出现，在成年左心房中含量相对较高。心脏内源性肾上腺素能细胞分布于整个成年心肌，包含合成E所需的所有酶。PNMT基因启动子区域含有一个糖皮质激素反应元件；然而，脑和心脏胎儿PNMT的初始发育不依赖糖皮质激素。大鼠胎儿心脏PNMT在胚胎第11天达到峰值，到第12天对糖皮质激素诱导变得敏感。在心脏发育过程中，含PNMT的细胞集中在房室管和室间隔，这些区域对心脏传导系统的发育很重要。在成年大鼠中，心脏PNMT可被糖皮质激素诱导并合成E。糖皮质激素对肾上腺中高水平PNMT的发育至关重要，但在肾上腺外则不太重要。PNMT基因包含3个外显子和2个内含子。肾上腺PNMT mRNA以单一类型存在，但在心脏中PNMT mRNA以无内含子和含内含子两种类型存在。在一些心脏组织中，糖皮质激素会降低含内含子的PNMT mRNA水平，增加无内含子的PNMT mRNA水平和PNMT活性。对肾上腺切除动物的研究表明，肾上腺外PNMT可升高血压、血糖和淋巴细胞细胞因子的产生。PNMT在肾上腺髓质发育之前对胎儿心率的调节中可能也起作用。
