Endopeptidases (kininases) are able to hydrolyze kinins in tubular fluid along the rat nephron.
The activities of serine endopeptidase, prolyl endopeptidase and neutral endopeptidase were determined in tubular fluid collected from several portions of the rat nephron as well as in urine. The enzyme activities were measured by HPLC using bradykinin (BK) as substrate. Free residual peptides of BK obtained by the action of these enzymes on the locally produced BK were also determined. The endopeptidase activities were found to be present throughout the nephron. Equimolar fragments of BK were detected in the early proximal tubule (Arg(1)-Pro(7), Phe(8)-Arg(9), Arg(1)-Gly(4), Phe(5)-Arg(9), and BK), late proximal tubule (Arg(1)-Phe(5), Arg(1)-Pro(7), Gly(4)-Pro(7), Gly(4)-Arg(9), and BK), late distal tubule (Arg(1)-Gly(4), Phe(5)-Arg(9), Arg(1)-Phe(5), Ser(6)-Arg(9), Gly(4)-Arg(9), BK, and [des-Arg(9)]BK) and urine (Phe(8)-Arg(9), Phe(5)-Arg(9), Arg(1)-Phe(5), Ser(6)-Arg(9), Arg(1)-Pro(7), Gly(4)-Pro(7), Gly(4)-Arg(9), BK, and [des-Arg(9)]BK). Our data suggest that the endopeptidases and exopeptidases are secreted by the nephron. Early proximal tubules secrete angiotensin converting enzyme and neutral endopeptidase, differing from late distal tubules that produce prolyl endopeptidase, serine endopeptidase, carboxypeptidase, and also neutral endopeptidase. All enzymes detected along the rat nephron were found in the urine. The existence of endopeptidases and carboxypeptidase in the distal nephron may have a potential physiological role in the inactivation of the kinins formed by kallikrein in the kidney and also in the inactivation of additional peptides other than BK.
Departamento de Medicina, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, CEP 04023-900, Brazil.
D E
DE
Casarini
M A
MA
Boim
R C
RC
Stella
N
N
Schor
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001826:Body Fluids / Q000737:chemistry / Q000201:enzymology*; D001920:Bradykinin / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism*; D006868:Hydrolysis; D007705:Kinins / Q000378:metabolism*; D008297:Male; D009399:Nephrons / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D007705:Kinins; D010450:Endopeptidases; D001920:Bradykinin