中性金属内肽酶（NEP）（EC 3.4.24.11）是心房利钠肽的主要降解酶，其在大鼠肾脏中的分布与抑制作用。

Distribution and inhibition of neutral metalloendopeptidase (NEP) (EC 3.4.24.11), the major degradative enzyme for atrial natriuretic peptide, in the rat kidney.

Kanazawa M, Johnston C I

Melbourne University, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.

Clin Exp Pharmacol Physiol. 1991 Jun;18(6):449-53. doi: 10.1111/j.1440-1681.1991.tb01477.x.

Abstract

Atrial natriuretic peptide (ANP) is degraded by neutral metalloendopeptidase (NEP) (EC 3.4.24.11) and the kidney is a major site of ANP clearance. 2. The regional distribution of NEP in the rat kidney was investigated. 3. The activity of NEP, measured with an enzymatic fluorimetric method employing N-dansyl-D-alanyl-glycyl-L-4-nitrophenylalanyl-glycine as a synthetic substrate, was 18 times and eight times higher in the outer stripe of the medulla and inner cortex than in the outer cortex (OC). 4. Low concentrations of NEP were found in the OC, inner stripe and inner medulla. 5. NEP activity in the rat kidney was inhibited by the specific NEP inhibitors (SCH39370, phosphoramidon and thiorphan) at micromolar concentrations. 6. The present result suggests that degradation of ANP by NEP occurs mainly in the proximal tubules of the juxtamedullary nephrons, rather than cortical nephrons, and that the convoluted tubule in the OC is not a major site of location of NEP. 7. The relationship between NEP activities in the kidney in vitro and plasma clearance of ANP in vivo remains to be clarified.

摘要

心房利钠肽（ANP）由中性金属内肽酶（NEP）（EC 3.4.24.11）降解，肾脏是ANP清除的主要部位。2. 研究了NEP在大鼠肾脏中的区域分布。3. 以N-丹磺酰-D-丙氨酰-甘氨酰-L-4-硝基苯丙氨酰-甘氨酸作为合成底物，采用酶荧光法测定的NEP活性，在髓质外带和内皮质中分别比外皮质（OC）高18倍和8倍。4. 在OC、内带和内髓中发现低浓度的NEP。5. 大鼠肾脏中的NEP活性在微摩尔浓度下受到特异性NEP抑制剂（SCH39370、磷酰胺脒和噻吗洛尔）的抑制。6. 目前的结果表明，NEP对ANP的降解主要发生在近髓肾单位的近端小管，而非皮质肾单位，并且OC中的曲小管不是NEP的主要定位部位。7. 肾脏体外NEP活性与体内ANP血浆清除率之间的关系仍有待阐明。