Distribution of neutral endopeptidase activity along the rat and rabbit nephron

Neutral endopeptidase (NEP) activity was measured in various nephron segmen ts dissected from rat and rabbit kidney. In the rat, only the proximal stra ight 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 convolut ed 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/glome rulus). 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, resp ectively. Incubation of rat proximal tubules with phorbol 12-myristate 13-a cetate resulted in a 50% reduction in membrane-associated NEP activity. The results demonstrate that in both the rat and rabbit NEP is restricted to t he glomerulus and proximal tubule. This localized distribution of NEP and i ts potential regulation by the protein kinase C pathway may play a key role in determining local concentrations of important regulatory peptides in th e kidney.