Peptides from the N-terminus of the atrial natriuretic factor prohormone enhance guanylate cyclase activity and increase cyclic GMP levels in a wide variety of tissues.
Peptides from the N-terminus of the atrial natriuretic factor prohormone enhance guanylate cyclase activity and increase cyclic GMP levels in a wide variety of tissues.
复制标题
来自心房钠尿因子激素原 N 末端的肽可增强多种组织中鸟苷酸环化酶的活性并增加环 GMP 水平。
DOI：
10.1007/bf00230872
复制
发表时间：
1992
影响因子：
4.3
通讯作者：
Vesely,DL
中科院分区：
文献类型：
--
作者：
Vesely,DL
98个氨基酸(a.a.)126a.a.心钠素(ANF)前激素的N端含有三个多肽：a.A1-30(proANF 1-30)、a.a.31-67(proANF 31-67)和a.79-98(proANF 79-98)，它们的降压、钠和/或钾排泄特性与心房利钠因子相似(a.A99-126，原激素的C端)。ProANF 1-30和ProANF 31-67在血管和肾脏中都有不同于ANF的独立和独特的受体，以帮助介导上述效应。在细胞水平上，proANF 1-30、31-67和79-98以及ANF的作用是通过增强血管和肾脏中鸟苷环化酶(EC 4.6.1.2)-环状GMP系统而介导的。这些来自ANF前激素N端的多肽在人类和所有被测试的动物物种中正常循环。本研究的目的是确定这些多肽是否能够增强除肾脏和血管系统之外的其他组织中的鸟苷环化酶和/或腺苷环化酶。ProANF 1-30、proANF 31-67、proANF 79-98和ANF均可使大鼠的肺、肝、心脏和睾丸在100 nM浓度下增加2-3倍，但对脾、颗粒鸟苷环化酶无影响。剂量反应曲线显示，这些新发现的多肽对颗粒鸟苷环化酶活力的最大刺激作用是在它们的1μM浓度时，而当它们的浓度超过1μM时，活性不再增加。ProANF 1-30、proANF 31-67、proANF 79-98和ANF的颗粒鸟苷环化酶半数增强(EC50)分别出现在0.15±0.01、0.3±0.02、0.5±0.03和0.9±0.03 nM。ProANF 1-30、31-67、79-98和99-126(即ANF)均可增加肝、肺、小肠、心脏和睾丸组织切片中cGMP的水平，但不增加cAMP的水平。这些多肽都不能促进腺苷环化酶或可溶的100000 G形式的鸟苷环化酶。这些N端肽能够在多种组织中增强颗粒鸟苷环化酶的活性，这表明它们可能在比目前认为的更广泛的组织中发挥作用。
The 98 amino acid (a. a.) N-terminus of the 126 a. a. atrial natriuretic factor (ANF) prohormone contains three peptides consisting of a. a. 1–30 (proANF 1–30), a. a. 31–67 (proANF 31–67) and a. a. 79–98 (proANF 79–98) with blood pressure lowering, sodium and/or potassium excreting properties similar to atrial natriuretic factor (a. a. 99–126, C-terminus of prohormone). ProANF 1–30 and proANF 31–67 have separate and distinct receptors from ANF in both vasculature and in the kidney to help mediate the above effects. At the cellular level proANFs 1–30, 31–67, and 79–98 as well as ANF's effects are mediated by enhancement of the guanylate cyclase (EC 4.6.1.2) — cyclic GMP system in vasculature and in the kidney. These peptides from the N-terminus of the ANF prohormone circulate normally in man and in all animal species tested. The object of the present investigation was to determine if these peptides have the ability to enhance either guanylate cyclase and/or adenylate cyclase in a variety of other tissues in addition to kidney and vasculature. ProANF 1–30, proANF 31–67, proANF 79–98, and ANF all increased rat lung, liver, heart and testes, but not spleen, particulate guanylate cyclase 2- to 3-fold at their 100 nM concentrations. Dose response curves revealed that maximal stimulation of particulate guanylate cyclase activity by these newly discovered peptides was at their 1 μM concentrations, with no further increase in activity above their 1 μM concentrations. Half-maximal (EC50) enhancement of particulate guanylate cyclase occurred at 0.15 ± 0.01, 0.3 ± 0.02, 0.5 ± 0.03, and 0.9 ± 0.03 nM for proANF 1–30, proANF 31–67, proANF 79–98 and ANF, respectively. ProANFs 1–30, 31–67, 79–98, and 99–126 (i.e., ANF) each increased cyclic GMP but not cyclic AMP levels in tissue slices of liver, lung, small intestine, heart, and testes. None of these peptides enhanced either adenylate cyclase or the soluble 100,000 G form of guanylate cyclase. The ability of these N-terminal peptides to enhance particulate guanylate cyclase activity in a wide variety of tissues suggests that they may have effects in a much wider variety of tissues than presently thought.