Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.
Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.
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在体外和体内通过血浆快速酶促降解生长激素释放激素，形成在 NH2 末端裂解的无生物活性产物。
DOI：
10.1172/jci112679
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Felix,AM
中科院分区：
文献类型：
--
作者：
Frohman,LA;Downs,TR;Williams,TC;Heimer,EP;Pan,YC;Felix,AM
采用高效液相色谱法（HPLC）、放射免疫法（RIA）和生物测定法检测了血浆对人生长激素释放激素（GRH）降解的影响。GRH(1-44)-NH2与人血浆孵育时，总GRH免疫反应的t1/2为63 min （RIA）。然而，HPLC显示GRH(1-44)-NH2的消失速度更快（t1/2, 17 min），这与一种疏水性较低但相对稳定的肽的出现有关，该肽具有完全的免疫反应性。序列分析表明其结构为GRH(3-44)-NH2。通过高效液相色谱法对纯化肽和合成肽进行共洗脱，也证实了其鉴定。GRH(3-44)-NH2的生物活性小于GRH(1-44)-NH2的10（-3）。正常人静脉注射GRH(1-44)-NH2后，在1 min内出现与GRH(3-44)-NH2保持相当的血浆免疫反应峰，GRH(1-44)-NH2 （HPLC）的t1/2为6.8 min。该结果为血浆二肽氨基肽酶灭活GRH提供了证据，可以限制其对垂体的作用。
The effect of plasma on degradation of human growth hormone-releasing hormone (GRH) was examined in vitro and in vivo using high performance liquid chromatography (HPLC), radioimmunoassay (RIA), and bioassay. When GRH(1-44)-NH2 was incubated with human plasma, the t1/2 of total GRH immunoreactivity was 63 min (RIA). However, HPLC revealed a more rapid disappearance (t1/2, 17 min) of GRH(1-44)-NH2 that was associated with the appearance of a less hydrophobic but relatively stable peptide that was fully immunoreactive. Sequence analysis indicated its structure to be GRH(3-44)-NH2. Identity was also confirmed by co-elution of purified and synthetic peptides on HPLC. Biologic activity of GRH(3-44)-NH2 was less than 10(-3) that of GRH(1-44)-NH2. After intravenous injection of GRH(1-44)-NH2 in normal subjects, a plasma immunoreactive peak with HPLC retention comparable to GRH(3-44)-NH2 was detected within 1 min and the t1/2 of GRH(1-44)-NH2 (HPLC) was 6.8 min. The results provide evidence for GRH inactivation by a plasma dipeptidylaminopeptidase that could limit its effect on the pituitary.