Laboratory Investigation

Kidney International (1982) 22, 331–337; doi:10.1038/ki.1982.177

Kallikrein and prekallikrein of the isolated basolateral membrane of rat kidney

Kenichi Yamada1 and Ervin G Erdös1

1Departments of Pharmacology and Internal Medicine, University of Texas Health Science Center, Dallas, Texas

Correspondence: Dr E G Erdös, Department of Pharmacology, University of Texas Health Science Center, 5323 Harry Hines, Dallas, Texas 75235, USA

Received 11 January 1982; Revised 18 March 1982.

Top

Abstract

Kallikrein and prekallikrein of the isolated basolateral membrane of rat kidney. A basolateral membrane (BLM) enriched fraction of the homogenized rat kidney contained kallikrein and prekallikrein which differ from urinary kallikrein. Triton X-100 (0.1%) or melittin (10-7 – 10-5 M) solubilized the membrane-bound enzyme. Prekallikrein was activated by trypsin and plasmin. Active kallikrein and activated prekallikrein cleaved the chromogenic substrate S-2266 and released bradykinin from kininogen. Aprotinin and antiserum to rat urinary kallikrein inhibited BLM kallikrein. Gel electrophoresis separated activated BLM prekallikrein and kallikrein; prekallikrein even after activation moved slower (Rf = 0.3) in electrophoresis at an alkaline pH than active kallikrein (Rf = 1). Gel filtration resolved BLM kallikrein to two proteins of low (4 times 104 M) and high (1.5 times 105 M) molecular weight. After isoelectric focusing of the activated BLM fraction, two kallikreins with pIs of 3.9 and 5.3 were obtained. The BLM fraction also contained renin which became active after Triton treatment. Renin activity was not enhanced by trypsin or acid pH indicating that there was no prorenin present. Thus, BLM of rat kidney contains a kallikrein which is different from urinary kallikrein. This kallikrein, when released from basal membrane, may appear in renal lymph and venous effluent.

Kallikréine et prékallikréine dans les membranes basolatérales isolées de reins de rat. Une fraction enrichie en membranes basolatérales (BLM) de reins homogénéisés de rat contenait une kallikréine et une prékallikréine différentes de la kallikréine urinaire. Le Triton X-100 (0,1%) et la mélittine (10-7 – 10-5 M) solubilisaient l'enzyme liée aux membranes. La prékallikréine était activée par la trypsine et par la plasmine. La kallikréine active et la prékallikréine activée clivaient le substrat chromogène S-2266 et libéraient de la bradykinine à partir du kininogène. L'aprotinine et un antisérum contre la kallikréine urinaire de rat inhibaient la kallikréine des BLM. L'électrophorèse sur gel a permis de séparer la prékallikréine activée de BLM et la kallikréine; la prékallikréine migrait plus lentement (Rf = 0,3) même après activation en électrophorèse à un pH alcalin que la kallikréine active (Rf = 1). La filtration sur gel a séparé la kallikréine de BLM en deux protéines de faible (4 times 104 M) et de fort (1,5 times 105 M) poids moléculaires. Après focalisation isoélectrique de la fraction activée de BLM, deux kallikréines de pI 3,9 et 5,8 ont été obtenues. La fraction de BLM contenait également de la rénine qui devenait active après traitement au Triton. L'activité rénine n'était pas stimulée par la trypsine ni par un pH acide, indiquant qu'il n'y avait pas de prorénine présente. Ainsi les BLM de reins de rat contiennent une kallikréine différente de la kallikréine urinaire. Cette kallikréine, lorsqu'elle est relarguée des membranes basales, pourrait apparaître dans la lymphe et l'effluent veineux rénaux.

Top

References

  1. Carretero OA, Scicli AG: The renal kallikrein-kinin system. Am J Physiol 238:F247–F255, 1980 | PubMed | ISI | ChemPort |
  2. Margolius HS: The kallikrein-kinin system, renal function and hypertensive diseases. Prog Biochem Pharmacol 17:116–122, 1980
  3. Mills I, MacFarlane N, Ward P, Obika L: The renal kallikrein-kinin system and the regulation of salt and water excretion. Fed Proc 35:181–188, 1976
  4. Roblero J, Garcia H, Corthorn J, Devito E: Kallikrein-like activity in perfusates and urine of isolated rat kidneys. Am J Physiol 231:1383–1389, 1976
  5. Levy SB, Lilley JJ, Frigon RP, Stone RA: Urinary kallikrein and plasma renin activity as determinants of renal blood flow. J Clin Invest 60:129–138, 1977 | PubMed | ChemPort |
  6. Levinsky NG: The renal kallikrein-kinin system. Circ Res 44:441–451, 1979 | PubMed |
  7. Suzuki S, Franco-Saenz R, Mulrow PJ, McPartland RP, Sustarsic D, Rapp JP: Effects of rat urinary arginine esterases on rat kidney to release renin. Endocrinology 108:1639–1642, 1981
  8. Sealey JE, Atlas SA, Laragh JH: Prorenin and other large molecular weight forms of renin. Endocr Rev 1:365–391, 1980 | PubMed |
  9. Schalekamp MADH, Derkx FHM: Plasma kallikrein and plasmin as activators of prorenin: Links between the renin-angiotensin system and other proteolytic systems in plasma. Clin Sci 61:15–21, 1981
  10. Werle E, Erdös EG: Über eine neue blutdrucksenkende, darmund uteruserregende Substanz im menschlichen Urin. Arch exper Path u Pharmakol 223:234–243, 1954
  11. Miwa I, Erdös EG, Seki T: Separation of peptide components of urinary-kinin (Substance Z). Proc Soc Exp Biol Med 131:768–772, 1969
  12. McGiff JC, Quilley J: Prostaglandins, kinins and the regulation of blood pressure. Clin Exp Hypertens 2:729–740, 1980
  13. Nasjletti A, McGiff JC, Coline-Chourio J: Interrelationship of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids. Circ Res 43:799–807, 1978
  14. Ward PE, Erdös EG, Gedney CD, Dowben RM, Reynolds RC: Isolation of membrane-bound renal enzymes that metabolize kinins and angiotensins. Biochem J 157:643–650, 1976
  15. Chao J, Margolius HS: Studies on rat renal cortical cell kallikrein. II. Identification of kallikrein as an ecto-enzyme. Biochim Biophys Acta 570:330–340, 1979
  16. Scicli AG, Gandolfi R, Carretero OA: Site of formation of kinins in the dog nephron. Am J Physiol 234:F36–F40, 1978 | PubMed | ISI | ChemPort |
  17. Nishimura K, Ward P, Erdös EG: Kallikrein and renin in the membrane fractions of the rat kidney. Hypertension 2:538–595, 1980
  18. Nishimura K, Alhenc-Gelas F, White A, Erdös EG: Activation of membrane-bound kallikrein and renin in the kidney. Proc Natl Acad Sci USA 77:4975–4978, 1980 | PubMed | ChemPort |
  19. Yamada K, Schulz WW, Page DS, Erdös EG: Kallikrein and prekallikrein on the basolateral membrane of rat kidney tubules. Hypertension 3:59–64, 1981
  20. Yamada K, Saito Y, Tamura Y, Yamamoto M, Kumagai A: Effects of antibody to renal plasma membrane on urinary excretion of adenosine 3',5'-monophosphate and phosphate induced by parathyroid hormone infusion in rats. Endocrinology 106:973–978, 1980
  21. Nishimura K, Erdös EG: Membrane bound kininase and kallikrein, in 8th Workshop Conference Hoechst-Enzymatic Release of Vasoactive Peptides, edited by Gross F, Vogel HG. New York, Raven Press, 1980, pp. 225–239
  22. Seki T, Nakajama T, Erdös EG: Colon kallikrein, its relation to the plasma enzyme. Biochem Pharmacol 21:1227–1235, 1972
  23. Erdös EG, Renfrew AG, Sloane EM, Wohler JR: Enzymatic studies on bradykinin and similar peptides. Ann NY Acad Sci 104:222–234, 1963
  24. Dale G, Latner AL: Isoelectric focusing in polyacrylamide gels. Lancet 1:847–848, 1968
  25. Righetti PG, Drysdale JW: Isoelectric focusing in gels. J Chromatogr 98:271–321, 1974
  26. Hirose S, Naruse M, Ohtsuki K, Inagami T: Totally inactive renin zymogen and different forms of active renin in hog brain tissues. J Biol Chem 256:5572–5576, 1981
  27. Slater EE, Haber E: Inactive renin—"Through a glass darkly". N Engl J Med 301:429–431, 1979
  28. Atlas SA, Laragh JH, Sealey JE, Hesson TE: An inactive prorenin-like substance in human kidney and plasma. Clin Sci 59:29S–33S, 1980
  29. Zimmermann Z, Geiger R, Kortmann H: Similarity between a kininogenase (kallikrein) from human large intestine and humanurinary kallikrein. Hoppe-Seyler's Z Physiol Chem 360:1767–1773, 1979
  30. Alhenc-Gelas F, Marchetti J, Allegrini J, Corvol P, Menard J: Measurement of urinary kallikrein activity, species differences in kinin production. Biochem Biophys Acta 677:477–488, 1981
  31. Fiedler F: Enzymology of glandular kallikrein, in Supplement to Handbook of Experimental Pharmacology, edited by Erdös EG, Heidelberg, Springer–Verlag, 1979, vol. 25, pp. 103–161
  32. Orstavik TB, Nustad K, Brandtzaeg P, Pierce JV: Cellular origin of urinary kallikreins. J Histochem Cytochem 24:1037–1039, 1976 | PubMed |
  33. Simpson JAV, Spicer SS, Chao J, Grimm L, Margolius HS: Kallikrein localization in rodent salivary glands and kidney with the immunoglobulin enzyme bridge technique. J Histochem Cytochem 27:1567–1576, 1979
  34. Orstavik TB: The kallikrein-kinin system in exocrine organs. J Histochem Cytochem 28:881–889, 1980 | PubMed | ISI | ChemPort |
  35. Kerbiriou DM, Bouma BN, Griffin JH: Immunochemical studies of human high molecular weight kininogen and of its complexes with plasma prekallikrein or kallikrein. J Biol Chem 255:3952–3958, 1980
  36. Movat HZ: The plasma kallikrein-kinin system and its interrelationship with other components of blood, in Supplement to Handbook of Experimental Pharmacology edited by Erdös EG, Heidelberg, Springer–Verlag, 1979, vol. 25, pp. 1–89
  37. Heidrich HG, Geiger R: Kininogenase activity in plasma membranes and cell organelles from rabbit kidney cortex: Subcellular localization of renal kallikrein by free-flow electrophoresis and density-gradient fractionation. Kidney Int 18:77–85, 1980

Extra navigation

.
ADVERTISEMENT