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人类体内非肾上腺生成肾上腺素的酶。特性、分布、调节及其与肾上腺素水平的关系。

Nonadrenal epinephrine-forming enzymes in humans. Characteristics, distribution, regulation, and relationship to epinephrine levels.

作者信息

Kennedy B, Bigby T D, Ziegler M G

机构信息

Department of Medicine, University of California, San Diego Medical Center 92103-8341, USA.

出版信息

J Clin Invest. 1995 Jun;95(6):2896-902. doi: 10.1172/JCI117996.

DOI:10.1172/JCI117996
PMID:7769131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC295977/
Abstract

Animal studies indicate that nonadrenal tissues may synthesize epinephrine (E). Here we demonstrate phenylethanolamine N-methyltransferase (PNMT) and/or nonspecific N-methyltransferase (NMT) enzymatic activity in human lung, kidney, heart, liver, spleen, and pancreas. There was a significant overall correlation (r = 0.34) between tissue PNMT and E. PNMT and NMT in human tissues differed in substrate and inhibitor specificity, thermal stability, and antigenicity. By these criteria, PNMT in human lung and in human bronchial epithelial cells were indistinguishable from adrenal PNMT. PNMT and/or NMT activity were present in red blood cells (RBCs), and cancer cell lines. Human kidney, lung, and pancreas showed immunohistochemical staining with an antibody to adrenal PNMT. RBC PNMT activity was lower in males than females and was increased in hyperthyroidism and decreased in hypothyroidism. PNMT activity in a human bronchial epithelial cell line was dramatically increased by incubation with dexamethasone. E and 3H-E levels in plasma and urine during an intravenous infusion of 3H-E into humans indicated that kidney may synthesize half of urinary E. We conclude that PNMT and NMT are widely distributed in human tissues, that they may synthesize E in vivo and are influenced by glucocorticoid and thyroid hormones.

摘要

动物研究表明,非肾上腺组织可能合成肾上腺素(E)。在此我们证明了人肺、肾、心脏、肝脏、脾脏和胰腺中存在苯乙醇胺N-甲基转移酶(PNMT)和/或非特异性N-甲基转移酶(NMT)的酶活性。组织PNMT与E之间存在显著的总体相关性(r = 0.34)。人组织中的PNMT和NMT在底物和抑制剂特异性、热稳定性及抗原性方面存在差异。根据这些标准,人肺和人支气管上皮细胞中的PNMT与肾上腺PNMT无法区分。PNMT和/或NMT活性存在于红细胞(RBC)及癌细胞系中。人肾、肺和胰腺经肾上腺PNMT抗体免疫组化染色呈阳性。男性红细胞PNMT活性低于女性,甲状腺功能亢进时升高,甲状腺功能减退时降低。人支气管上皮细胞系中的PNMT活性经地塞米松孵育后显著增加。在向人体静脉输注3H-E期间,血浆和尿液中的E及3H-E水平表明,肾脏可能合成了一半的尿E。我们得出结论,PNMT和NMT广泛分布于人体组织中,它们可能在体内合成E,并受糖皮质激素和甲状腺激素影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/99022243bb7a/jcinvest00027-0482-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/538b7d9fbf52/jcinvest00027-0480-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/5158a7510924/jcinvest00027-0481-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/99022243bb7a/jcinvest00027-0482-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/538b7d9fbf52/jcinvest00027-0480-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/5158a7510924/jcinvest00027-0481-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/295977/99022243bb7a/jcinvest00027-0482-a.jpg

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Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine -Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains.基于结构的苯乙胺-N-甲基转移酶双底物抑制剂的药物设计,该抑制剂对两个底物结合域均具有低纳摩尔亲和力。
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