Kennedy B, Elayan H, Ziegler M G
Department of Medicine, University of California San Diego Medical Center 92103.
Am J Hypertens. 1991 Jan;4(1 Pt 1):45-50. doi: 10.1093/ajh/4.1.45.
Carotid artery and aorta homogenates synthesized epinephrine (E) from norepinephrine (NE) in the presence of S-adenosylmethionine. Aorta synthesized epinine by the N-methylation of dopamine (DA) about 3 times as well as it synthesized E from NE. In contrast, adrenal homogenates which contain phenylethanolamine N-methyltransferase (PNMT) methylated DA only 1% as well as NE. The PNMT inhibitor SKF 29661 had no significant effect on methylation of NE by aorta but inhibited adrenal PNMT by 88%. N-Methylating activity in arterial homogenates was increased by dexamethasone and following catecholamine depletion by 6-hydroxydopamine (6-OHDA) and reserpine. Nine days after adrenal demedullation blood E levels collected at decapitation were less than 7% of levels found in sham operated controls but artery homogenate E was unchanged. Demedullated rats given 6-OHDA followed by reserpine for 4 days also had unchanged arterial E levels despite arterial NE levels that were less than 15% of controls. We conclude that arteries synthesize E in vitro and appear to synthesize E in vivo using an extraneuronal N-methyltransferase. This enzyme differs from adrenal PNMT in substrate and inhibitor specificity and its activity is enhanced by catecholamine depletion and by glucocorticoid treatment.
在S-腺苷甲硫氨酸存在的情况下,颈动脉和主动脉匀浆可将去甲肾上腺素(NE)合成肾上腺素(E)。主动脉通过多巴胺(DA)的N-甲基化合成去甲伪麻黄碱的能力约为其将NE合成E能力的3倍。相比之下,含有苯乙醇胺N-甲基转移酶(PNMT)的肾上腺匀浆将DA甲基化的能力仅为将NE甲基化能力的1%。PNMT抑制剂SKF 29661对主动脉将NE甲基化的过程没有显著影响,但可使肾上腺PNMT的活性降低88%。地塞米松可增强动脉匀浆中的N-甲基化活性,6-羟基多巴胺(6-OHDA)和利血平使儿茶酚胺耗竭后,该活性也会增强。肾上腺髓质切除9天后,断头时采集的血液中E水平低于假手术对照组的7%,但动脉匀浆中的E水平未发生变化。给去髓质大鼠注射6-OHDA,随后注射利血平4天,尽管动脉NE水平低于对照组的15%,但动脉E水平仍未改变。我们得出结论,动脉在体外可合成E,并且在体内似乎是利用一种非神经元N-甲基转移酶来合成E的。这种酶在底物和抑制剂特异性方面与肾上腺PNMT不同,其活性可通过儿茶酚胺耗竭和糖皮质激素处理而增强。