Degradation and transport of AVP by proximal tubule.
Degradation and transport of AVP by proximal tubule.
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AVP 被近端小管降解和转运。
DOI：
10.1152/ajprenal.1987.253.6.f1120
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Flouret,G
中科院分区：
文献类型：
--
作者：
Carone,FA;Christensen,EI;Flouret,G
高效液相色谱（HPLC）分析显示，[3，4，5 - 3 H-Phe 3，Arg 8]加压素（[3 H]AVP）不降解分离的肾刷状缘膜或皮质溶酶体馏分在体外，然而，在1 mM还原型谷胱甘肽的存在下，[3 H]AVP降解的两种制剂。体外肾皮质匀浆和体内近端小管的管腔肽酶降解[3 H]AVP，并在两种情况下产生苯丙氨酸、六肽AVP 1-6、七肽AVP 1-7、八肽AVP 1-8和两种未表征的产物X和Y。这些数据表明，过滤的AVP减少在近端小管中的谷胱甘肽依赖性转氢酶减少，随后裂解为[3 H]苯丙氨酸由管状氨肽酶。[3 H]AVP微量注入近端小管后，15.7%的标记物被吸收。输注[3 H]AVP后5分钟和15分钟，近端小管中总标记的隔离分别为4.5%和2.1%，定量电子显微镜放射自显影显示颗粒在顶端内吞空泡和溶酶体上的积累与AVP和/或大代谢物的内吞摄取和快速溶酶体降解一致。因此，近端小管中的管腔和溶酶体肽酶对AVP的酶促裂解可能涉及二硫键、C-末端和N-末端位点。
High-performance liquid chromatography (HPLC) analysis revealed that [3,4,5-3H-Phe3,Arg8]vasopressin ([3H]AVP) was not degraded by isolated renal brush-border membranes or by a cortical lysosomal fraction in vitro; however, in the presence of 1 mM reduced glutathione, [3H]AVP was degraded by both preparations. Renal cortical homogenates in vitro and luminal peptidases of proximal tubule in vivo degraded [3H]AVP and in both instances yielded phenylalanine, hexapeptide AVP 1-6, heptapeptide AVP 1-7, octapeptide AVP 1-8, and two uncharacterized products X and Y. These data suggest that filtered AVP is reduced in the proximal tubule by a reduced glutathione-dependent transhydrogenase and subsequently cleaved to [3H]Phe by tubular aminopeptidases. Following microinfusion of [3H]AVP into proximal tubules, 15.7% of the label was absorbed. Five and fifteen minutes after infusion of [3H]AVP, sequestration of total label in proximal tubules was 4.5 and 2.1%, respectively, and quantitative electron microscope autoradiography revealed accumulation of grains over apical endocytic vacuoles and lysosomes consistent with endocytic uptake and rapid lysosomal degradation of AVP and/or a large metabolite. Thus, enzymatic cleavage of AVP by luminal and lysosomal peptidases in proximal tubules could involve disulfide bond, C-terminal, and N-terminal loci.