Abstract
Kinins are vasoactive paracrine peptides which participate in a wide range of functions, including the regulation of local organ blood flow, systemic blood pressure, transepithelial water and electrolyte transport, cellular growth, capillary permeability and inflammatory response, and pain. The recent introduction of specific bradykinin receptor subtype antagonists has greatly advanced our understanding of the role of the kallikrein-kinin system (KKS) in various physiological and disease states. However, a major gap remains in our knowledge of the role of kinins in early development. In this review, evidence is presented that the developing nephron expresses both tissue kallikrein and kininogen, and that the genes encoding the components of the KKS are subject to considerable developmental regulation. The activity of the intrarenal kinin-generating system is lowest in the developing kidney and increases with age. Completion of nephrogenesis is characterized by a marked surge in intrarenal kallikrein synthesis and gene transcription. Maturation is associated with redistribution of intrarenal kallikrein and its messenger RNA from the inner to outer cortical nephrons following the centrifugal pattern of nephron development. Challenges for the future include delineation of the direct role of kinins in the maturation of renal functions and elucidation of the molecular mechanisms underlying the developmental expression of the KKS.
Similar content being viewed by others
References
Abelous JE, Bardier E (1909) Les substances hypotensive de l'urine humaine normale. C R Soc Biol Paris 66:511–512
Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens and kininases. Pharmacol Rev 44:1–80
Howard EC, Spitzer A (1992) Renal blood flow and glomerular filtration rate during development. In: Edelmann CM (ed), 2nd edn. Pediatric kidney disease. Little Brown, Boston, pp 49–77
Fenoy FJ, Scicli G, Carretero O, Roman RJ (1991) Effect of angliotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril. Hypertension 17:1038–1044
Robillard JE, Weismann DN, Gomez RA, et al (1983) Renal and adrenal responses to converting enzyme inhibition in fetal and newborn life. Am J Physiol 244:R249-R256
Robillard JE, Lawton WJ, Weismann DN, Sessions C (1982) Developmental aspects of the renal kallikrein-like activity in fetal and newborn lambs. Kidney Int 22:594–601
Issandou M, Darbon J-M (1991) Des-Arg9 bradykinin modulates DNA synthesis, phospholipase C, and protein kinase C in cultured mesangial cells. J Biol Chem 266:21037–21043
Farhy RD, Ho KL, Carretero OA, Scicli AG (1992) Kinins mediate the antiproliferative effect of ramipril in rat carotid artery. Biochem Biophys Res Commun 182:283–288
Linz W, Scholkens BA (1992) A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 105:771–772
Seidah NG, Ladenheim R, Mbikay M, et al (1989) The cDNA structure of rat plasma kallikrein. DNA 8:563–574
Mandle R Jr, colman RW, Kaplan AP (1976) Identification of prekallikrein and HMW-kininogen as a circulating complex in human plasma. Proc Natl Acad Sci USA 73:4179–4183
Kaplan AP, Silverberg M (1987) The coagulation-kinin pathway of human plasma. Blood 70:1–16
Richards RI, Catanzaro DF, Mason AJ, et al. (1982) Mouse glandular kallikrein genes. J Biol Chem 257:2758–2762
Evans BA, Drinkwater CC, Richards RI (1987) Mouse glandular kallikreins genes. Structure and partial sequence analysis of the kallikrein gene locus. J Biol Chem 262:8027–8034
Ashley PL, MacDonald RJ (1985) Tissue-specific expression of kallikrein-related genes in the rat. Biochemistry 24:4520–4527
Gerald WL, Chao J, Chao L (1986) Immunological identification of rat tissue kallikrein cDNA and characterization of the kallikrein gene family. Biochim Biophys Acta 866:1–14
Chen Y, Chao J, Chao L (1988) Molecular cloning and characterization of two rat renal kallikrein genes. Biochemistry 27:7189–7196
Fukushima D, Kitamura N, Nakanishi S (1985) Nucleotide sequence of cloned cDNA for human pancreatic kallikrein. Biochemistry 24: 8037–8043
Murray SR, Chao J, Lin FK, Chao L (1990) Kallikrein multigene families and the regulation of their expression. J Cardiovasc Pharmacol 15 [Suppl 6]:S7-S16
Wines DR, Brady JM, Southard EM, MacDonald RJ (1991) Evolution of the rat kallikrein gene family: gene conversion leads to functional diversity. J Mol Evol 32:476–492
Chao J, Chao L, Swain CC, Tsai J, Margolius HS (1987) Tissue kallikrein in rat brain and pituitary: regional distribution and estrogen induction in the anterior pituitary. Endocrinology 120:475–482
Clements JA, Fuller PJ, McNally M, Nikolaidis I, Funder JW (1986) Estrogen regulation of kallikrein gene expression in the rat anterior pituitary. Endocrinology 119:268–273
Rosewicz S, Logson CD (1989) Pancreatic kallikrein gene expression: effects of glucocorticoids in vivo and in vitro. Gastroenterology 97:1005–1010
Gerald WL, Chao J, Chao L (1986) Sex dimorphism and hormonal regulation of rat tissue kallikrein mRNA. Biochim Biophys Acta 867:16–23
Chao J, Margolius HS (1983) Differential effects of testosterone, thyroxine, and cortisol on rat submandibular gland versus renal kallikrein. Endocrinology 113:2221–2225
Harvey JN, Jaffa AA, Sutherland S, Margolius HS, Mayfield RK (1989) Renal kallikrein responses to dietary protein: a possible mediator of hyperfiltration. Kidney Int 36:1003–1010
Miller DH, Chao J, Margolius HS (1984) Tissue kallikrein synthesis and its modification by testosterone or low dietary sodium. Biochem J 218:37–43
Inoue H, Fukui K, Miyake Y (1989) Identification and structure of the rat true tissue kallikrein gene expressed in the kidney. J Biochem 105:834–840
Swift GH, Dagorn JC, Ashley PL, Cummings SW, MacDonald RJ (1982) Rat pancreatic kallikrein mRNA: nucleotide sequence and amino acid sequence of the encoded preproenzyme. Proc Natl Acad Sci USA 79:7263–7267
Fuller PJ, Verity K, Matheson BA, Clements JA (1989) Kallikrein gene expression in the rat gastrointestinal tract. Biochem J 264: 133–136
Saed G, Carretero OA, MacDonald RJ, Scicli G (1990) Kallikrein messenger RNA in rat arteries and veins. Circ Res 67: 510–516
Fuller PJ, Clements JA, Whitfield PL, Funder JW (1985) Kallikrein gene expression in the rat anterior pituitary. Mol Cell Endocrinol 39: 99–105
El-Dahr SS, Chao J (1992) Spatial and temporal expression of kallikrein and its mRNA during nephron maturation. Am J Physiol 262: F705-F711
Xiong W, Chao L, Chao J (1989) Renal kallikrein mRNA localizaiton by in situ hybridization. Kidney Int 35: 1324–1329
Saed GM, Beierwaltes WH, Carretero OA, Scicli AG (1992) Submandibular enzymatic vasoconstrictor messenger RNA in the rat kidney. Hypertension 19 [Suppl II]: 262–267
Yamaguchi T, Carretro OA, Scicli (1991) A novel serine protease with vasoconstrictor activity coded by the kallikrein gene S3. J Biol Chem 266: 5011–5017
Brady JM, MacDonald RJ (1990) The expression of two kallikrein gene family members in the rat kidney. Arch Biochem Biophys 278: 342–349
Jian-Xing M, Chao J, Chao L (1992) Molecular cloning and characterization of rKLK10, a cDNA encoding T-kininogenase from submandibular gland and kidney. Biochemistry 31: 10922–10928
Boucher R, Asselin J, Genest J (1974) A new enzyme leading to the direct formation of angiotensin II. Circ Res 34/35 [Suppl I]: 203–209
Elmoujahed A, Gutman N, Brillard M, Gauthier F (1990) Substrate specificity of two kallikrein family gene products isolated from the rat submaxillary gland. FEBS Lett 265: 137–140
Berg T, Nustad K (1986) Enzymatic activity of rat submandibular gland kallikrein released into blood. Am J Physiol 249: H1134-H1142
Nolly H, Scicli A, Scicli G, Carretero OA (1985) Characterization of a kininogenase from rat vascular tissue resembling tissue kallikrein. Circ Res 56: 816–821
Oza NB, Schwartz JH, Goud MD, Levinsky NG (1990) Rat aortic smooth muscle cells in culture express kallikrein, kininogen and bradykininase activity. J Clin Invest 85: 597–600
Figueroa CD, Maciver AG, Bhoola KD (1989) Identification of tissue kallikrein in human polymorphonuclear leukocytes. Br J Haematol 72: 321–328
Ole-Moiyoi O, Seldin DC, Spragg J, Pinkus G, Austen KF (1979) Sequential cleavage of pro-insulin by human pancreatic kallikrein and a human pancreatic kinase. Proc Natl Acad Sci USA 76: 3612–3616
Currie MG, Gellen DM, Chao J, Margolius HS, Needleman P (1984) Kallikrein activation of a high molecular weight atrial peptide. Biochem Biophys Res Commun 120: 461–466
Cardin AC, Witt KR, Chao J, Margolius HS, Donaldson VH, Jackson RL (1984) Degradation of apolipoprotein B-100 of human plasma low density lipoprotein by tissue and plasma kallikrein. J Biol Chem 259: 8522–8228
Mutt V, Said SI (1974) Structure of porcine vasoactive intestinal octacosapeptide. The amino-acid sequence. Use of kallikrein in its determination. Eur J Biochem 42: 581–589
Arakawa K, Maruta H (1990) Ability of kallikrein to generate angliotensin II-like pressor substance and a proposed “kinin-tensin enzyme system”. Nature 288: 705–706
Clements JA, Matheson BA, Funder JW (1990) Tissue-specific developmental expression of the kallikrein gene family in the rat. J Biol Chem 265: 1077–1081
Evan AP, Larsson L (1992) Morphologic development of the nephron. In: Edelmann CM (ed), 2nd edn. Pediatric kidney disease. Little Brown, Boston, pp 19–48
Penschow JD, Coghlan JP (1992) Sites of glandular kallikrein gene expression in fetal mice. Mol Cell Endocrinol 88: 23–30
Godard C, Valloton MB, Favre L (1982) Urinary prostaglandins, vasopressin and kallikrein excretion in healthy children from birth to adolescence. J Pediatr 100: 898–902
Vio CP, Olavarria F, Krause S, Hermann F, Grob K (1987) Kallikrein excretion: relationship with maturation and renal function in human neonates at different gestational ages. Biol Neonate 52: 121–126
Kellermann J, Thelen C, Lottspeich F, Henschen A, Vogel R, Muller-Esterl W (1987) Arrangement of the disulphide bridges in human low Mr kininogen. Biochem J 247: 15–21
Kitamura N, Takagaki Y, Furuto S, Tanaka T, Nawa H, Nakanishi S (1983) A single gene for bovine high molecular weight and low molecular weight kininogens. Nature 305: 545–549
Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, Nakanishi S (1985) Structural organization of the human kininogen gene and a model for its evolution. J Biol Chem 260: 8610–8617
Kakizuka A, Kitamura N, Nakanishi S (1988) Localization of DNA sequences governing alternative mRNA production on rat kininogen genes. J Biol Chem 263: 3884–3892
Kakizuka A, Ingi T, Murai T, Nakanishi S (1990) A set of U1 snRNA complementary sequences involved in governing alternative RNA splicing of the kininogen genes. J Biol Chem 265: 1–7
Chao J, Swain C, Chao S, Xiong W, Chao L (1988) Tissue distribution and kininogen gene expression after acute phase inflammation. Biochim Biophys Acta 964: 329–339
Xu J, Hsu CY, Junker H, Chao S, Hogan EL, Chao J (1991) Kininogen and kinin in experimental spinal cord injury. J Neurochem 57: 975–980
Sueyoshi T, Enjyoji K, Shimada T, Kato H, Iwanaga S, et al (1985) A new function of kininogens as thiol-proteinase inhibitors: inhibition of papain and cathepsins B, H and L by bovine, rat and human plasma kininogens. FEBS Lett 182: 193–195
Okamoto H, Greenbaum LM (1983) Pharmacological properties of T-kinin (isoleucyl-seryl-bradykinin) from rat plasma. Biochem Pharmacol 32: 2637–2638
Melmon KL, Cline MJ, Hughes T, Sies AS (1968) Kinins: possible mediators of neonatal circulatory changes in man. J Clin Invest 47: 1295–1302
Assali NS, Johnson GH, Brinkman CR, Huntsman DJ (1971) Effects of bradykinin on the fetal circulation. Am J Physiol 221: 1375–1382
Mann EA, Lingrel JB (1991) Developmental and tissue-specific expression of rat T-kininogen. Biochem Biophys Res Commun 174: 417–423
El-Dahr SS, Dipp S, Chao J (1992) Differential developmental expression of the rat kininogen genes. Pediatr Res 32: 649–653
Pround D, Perkins M, Pierce JV, Yates K, et al (1981) Characterization and localization of human renal kininogen. J Biol Chem 256: 10634–10639
Figueroa CD, Maciver AG, Mackenzie JC, Bhoola KD (1988) Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron. Histochemistry 89: 437–442
El-Dahr SS, Dipp S, Chao J (1991) Ontogeny of the intrarenal kallikrein-kinin system. Evidence for developmental regulation (abstract). Pediatr Res 29: 341
Bathon JM, Proud D (1991) Bradykinin antagonists. Annu Rev Pharmacol Toxicol 31: 129–162
Hock FJ, Wirth K, Albus U, Linz W, Gerhards HJ, et al (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol 102: 769–773
Wirth K, Hock FJ, Albus U, Linz W, et al (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies. Br J Pharmacol 102: 774–777
Bao G, Gohlke P, Qadri F, Unger T (1992) Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril. Hypertension 20: 74–79
Farmer SG, Burch RM, Kyle DJ, Martin JA, Meeker SN, Togo J (1991)d-Arg [Hyp3-Thi5-Tic7-Tic8]-bradykinin, a potent antagonist of smooth muscle BK2 receptors and BK3 receptors. Br J Pharmacol 102: 785–787
McEachern AE, Shelton ER, Bhakta S, Obernolte R, et al (1991) Expression cloning of a rat B2 bradykinin receptor. Proc Natl Acad Sci USA 88: 7724–7728
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
El-Dahr, S.S., Dipp, S. Molecular aspects of kallikrein and kininogen in the maturing kidney. Pediatr Nephrol 7, 646–651 (1993). https://doi.org/10.1007/BF00852573
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00852573