Edwards R M, Pullen M, Nambi P
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Pharmacology. 1999 Jul;59(1):45-50. doi: 10.1159/000028304.
Neutral endopeptidase (NEP) activity was measured in various nephron segments dissected from rat and rabbit kidney. In the rat, only the proximal straight tubule and glomerulus had measurable NEP activity of 86 +/- 11.3 pmol/min/mm tubule length and 5.8 +/- 1.5 pmol/min/glomerulus, respectively. In the rabbit, significant activity was observed in both the proximal convoluted tubule (70.8 +/- 7.2 pmol/min/mm) and proximal straight tubule (29.6 +/- 2.3 pmol/min/mm) as well as in the glomerulus (12.8 +/- 2.2 pmol/min/glomerulus). In the rat proximal tubule, phosphoramidon and thiorphan inhibited NEP activity, with IC50 values of 26.6 +/- 6.0 and 6.9 +/- 1.6 nmol/l, respectively. Incubation of rat proximal tubules with phorbol 12-myristate 13-acetate resulted in a 50% reduction in membrane-associated NEP activity. The results demonstrate that in both the rat and rabbit NEP is restricted to the glomerulus and proximal tubule. This localized distribution of NEP and its potential regulation by the protein kinase C pathway may play a key role in determining local concentrations of important regulatory peptides in the kidney.
在从大鼠和兔肾脏分离出的各个肾单位节段中测量了中性内肽酶（NEP）活性。在大鼠中，仅近端直管和肾小球具有可测量的NEP活性，分别为86±11.3 pmol/分钟/毫米肾小管长度和5.8±1.5 pmol/分钟/肾小球。在兔中，在近端曲管（70.8±7.2 pmol/分钟/毫米）、近端直管（29.6±2.3 pmol/分钟/毫米）以及肾小球（12.8±2.2 pmol/分钟/肾小球）中均观察到显著活性。在大鼠近端小管中，磷酰胺脒和硫磷酰胺抑制NEP活性，IC50值分别为26.6±6.0和6.9±1.6 nmol/L。用佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯孵育大鼠近端小管导致膜相关NEP活性降低50%。结果表明，在大鼠和兔中，NEP均局限于肾小球和近端小管。NEP的这种局部分布及其受蛋白激酶C途径的潜在调节可能在决定肾脏中重要调节肽的局部浓度方面起关键作用。
