Skip to main content
Log in

Renin processing studied by immunogold localization of prorenin and renin in granular juxtaglomerular cells in mice treated with enalapril

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

Immunogold techniques were used to investigate renin processing within granular juxtaglomerular cells following short-term (6 h and 1 day) and long-term (4 weeks) enalapril treatment in female BALB/c mice. In control animals, renin protein labelling was localized to all types of granules (proto-, polymorphous, intermediate and mature) and to transport vesicles, whilst prorenin labelling was found in all these sites except mature granules, confirming that active renin is localized to mature granules only. Following short-term enalapril treatment, the exocytosis of renin protein from mature granules was increased. Long-term enalapril treatment resulted in increased numbers of transport vesicles and all types of granules, consistent with increased synthesis and storage of renin. More large intermediate granules contained discrete regions labelled for prorenin. Renin protein was exocytosed from individual and multiple granules, whilst prorenin was exocytosed from protoand intermediate granules. It is concluded that under normal conditions prorenin is secreted constitutively by bulk flow from transport vesicles. On the other hand, active renin is secreted regulatively from mature granules. In conditions of intense stimulation (angiotensin-converting enzyme inhibition treatment), increased synthesis of prorenin leads to enhanced secretion of prorenin by both constitutive and regulative pathways. Under these conditions, the conversion of prorenin to active renin is increased, with increased secretion of active renin occurring in a regulative manner. Furthermore, the localization of prorenin to one discrete region of large intermediate granules leads us to conclude, that cleavage of the prosegment of renin occurs with the transition of intermediate to mature granules.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barajas L (1966) The development and ultrastructure of the juxtaglomerular cell granule. J Ultrastruct Res 15:400–413

    Google Scholar 

  • Barrett GL, Morgan TO, Smith M, Alcorn D, Aldred P (1989) Effect of converting enzyme inhibition on renin synthesis and secretion in mice. Hypertension 14:385–398

    Google Scholar 

  • Beresford WA (1990) Direct transdifferentiation: can cells change their phenotype without dividing? Cell Diff Dev 29:81–93

    Google Scholar 

  • Berka JLA, Alcorn D, Coghlan JP, Fernley RT, Morgan TO, Ryan GB, Skinner SL, Weaver DA (1990) Granular juxtaglomerular cells and prorenin synthesis in mice treated with enalapril. J Hypertens 8:229–238

    Google Scholar 

  • Do YS, MacCauley L, Anderson PM, Katterman J, Shaw K, Koss M, Hsueh WA (1989) Membrane-bound vesicles mediate constitutive secretion of human prorenin in extrarenal tissue (abstract). 71st Annual Meeting of The Endocrine Society, Seattle, Washington, USA, p 464

  • Fritz LC, Haidar MA, Arfsten AE, Schilling JW, Carilli C, Shine J, Baxter JD, Reudelhuber TL (1987) Human renin is correctly processed and targeted to the regulated secretory pathway in mouse pituitary AtT-20 cells. J Biol Chem 262:12409–12412

    Google Scholar 

  • Galen FX, Devaux C, Houot AM, Ménard J, Corvol P, Corvol MT, Grubler MC, Mounier F, Camilleri JP (1983) Renin biosynthesis by human tumoral juxtaglomerular cells. J Clin Invest 73:1144–1155

    Google Scholar 

  • Garrett JR, Harrop TJ, Kidd A, Thulin A (1977) Nerve-induced secretory changes in salivary glands. In: Brooks F, Evers W (eds). Nerves and the gut. CB Slack, Thorofare, pp 13–49

    Google Scholar 

  • Gomez RA, Lynch KR, Dhevalier RL, Everett AD, Johns DW, Wilfong N, Peach MJ, Carey RM (1988) Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition. Am J Physiol 254:F900-F906

    Google Scholar 

  • Higashimori K, Mizuno K, Nakajo S, Boehm FH, Marcotte PA, Egan DA, Holleman WH, Heusser C, Poisner AM, Inagami T (1989) Pure human inactive renin. Evidence that native inactive renin is prorenin. J Biol Chem 264:14662–14667

    Google Scholar 

  • Hirose S, Kim S-J, Miyazaki H, Park Y-S, Murakami K (1985) In vitro biosynthesis of human renin and identification of plasma inactive renin as an activation intermediate. J Biol Chem 260:16400–16405

    Google Scholar 

  • Ichikawa A (1965) Fine ultrastructural changes in response to hormonal stimulation in the perfused canine pancreas. J Cell Biol 24:369–385

    Google Scholar 

  • Kelly RB (1985) Pathways of secretion in eukaryotes. Science 230:25–32

    Google Scholar 

  • Kim SJ, Hirose S, Miyazaki H, Ueno N, Higashimori K, Morinaga S, Kimura T, Sakakibara S, Murakami K (1985) Identification of plasma inactive renin as prorenin with a site-directed antibody. Biochem Biophys Res Commun 126:641–645

    Google Scholar 

  • Lacasse J, Ballak M, Mecure G, Gutkowska J, Chapeau C, Foote S, Ménard J, Corvol P, Cantin M, Genest J (1985) Immunocytochemical localization of renin in juxtaglomerular cells. J Histochem Cytochem 33:323–332

    Google Scholar 

  • Latta H, Mausbach AB (1962) The juxtaglomerular apparatus as studied electron microscopically. J Ultrastruct Res 6:547–561

    Google Scholar 

  • Lee JC, Hurley S, Hopper J (1966) Secretory activity of the juxtaglomerular granular cells of the mouse. Morphologic and enzyme histochemical observations. Lab Invest 15:1459–1476

    Google Scholar 

  • Lindop GBM (1987) Morphological aspects of renin synthesis, processing, storage and secretion. Kidney Int 31 [Suppl 20]:S18-S24

    Google Scholar 

  • Matsuba H, Watanabe T, Watanabe M, Ishii Y, Waguri S, Kominami E, Uchiyama Y (1989) Immunocytochemical localization of prorenin, renin and cathepsin B, H and L in juxtaglomerular cells of rat kidney. J Histochem Cytochem 37:1689–1697

    Google Scholar 

  • Misono KS, Inagami T (1982) Structure of mouse submaxillary gland renin. Identification of two disulphide-linked polypeptide chains and the complete amino acid sequence of the light chain. J Biol Chem 257:7536–7540

    Google Scholar 

  • Nakamura N, Soubrier F, Ménard J, Panthier J-J, Rougeon F, Corvol P (1985) Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA. Hypertension 7:855–859

    Google Scholar 

  • Naruse K, Naruse M, Hirose S, Nagano M, Yamakado M, Kurimoto F, Sakurai H, Zeng Z-P, Demura H, Inagami T, Shizume K (1988) Immunoreactive prorenin and its profragment peptide are present in human juxtaglomerular cells. J Hypertens 6 [Suppl 4]:S426-S428

    Google Scholar 

  • Peter S (1967) Ultrastructural studies on the secretory process in the epithelioid cells of the juxtaglomerular apparatus. Cell Tissue Res 168:45–53

    Google Scholar 

  • Pollard HB, Pazoles C, Creutz CE (1981) Mechanism of calcium action and release of vesicle-bound hormones during exocytosis. Reg Prog Horm Res 37:299–325

    Google Scholar 

  • Pratt RE, Carleton JE, Richie JP, Heusser C, Dzau VJ (1987) Human renin biosynthesis and secretion in normal and ischemic kidneys. Proc Natl Acad Sci USA 84:7837–7840

    Google Scholar 

  • Pratt RE, Flynn JA, Hobart PM, Paul M, Dzau VJ (1988) Different secretory pathway of renin from mouse cells transfected with the human renin gene. J Biol Chem 263:3137–3141

    Google Scholar 

  • Rouiller C, Orci L (1971) The structure of the juxtaglomerular complex. In: Rouiller C, Muller AF (eds) The kidney, vol 5. Academic Press, London New York, pp 1–80

    Google Scholar 

  • Ryan GB, Alcorn D, Coghland JP, Hill PA, Jacobs R (1982) Ultrastructural morphology of granule release from juxtaglomerular myoepithelioid and peripolar cells. Kidney Int 22 [Suppl 12]:S3-S8

    Google Scholar 

  • Saruta T, Eguchi T, Yasui T, Nagahama S, Nakamura R, Kato E (1981) Effect of angiotensin I converting enzyme inhibitor, SQ 14225, on renin production and release. Nephron 29:265–269

    Google Scholar 

  • Senarclens CF de, Pricam CE, Banichahi FD, Vallotton MB (1977) Renin synthesis, storage and release in the rat: a morphological and biochemical study. Kidney Int 11:161–169

    Google Scholar 

  • Shinagawa T, Do YS, Baxter JD, Carilli C, Schilling J, Hsueh WA (1990) Identification of an enzyme in human kidney that correctly processes prorenin. Proc Natl Acad Sci USA 87:1927–1931

    Google Scholar 

  • Skøtt O (1986) Episodic release of renin from single isolated superfused afferent arterioles. Pflügers Arch 407:41–45

    Google Scholar 

  • Skøtt O, Taugner R (1987) Effects of extracellular osmolality on renin release and on ultrastructure of the juxtaglomerular epithelioid cell granules. Cell Tissue Res 249:325–329

    Google Scholar 

  • Szabo J, Devenji I (1972) Ultrastructural data on different types of hyperplasia and hyperfunction of the juxtaglomerular apparatus. Acta Morphol Hung 20:39–48

    Google Scholar 

  • Takahashi S, Murakami K, Mujake Y (1982) Activation of kidney prorenin by kidney cathepsin B and isoenzymes. J Biochem 91:419–422

    Google Scholar 

  • Tanaka Y, De Camilli P, Meldolesi J (1980) Membrane interactions between secretion granules and plasmalemma in three exocrine glands. J Cell Biol 84:438–453

    Google Scholar 

  • Taugner R, Marin-Grez M, Keilbach R, Hackenthal E, Nobiling R (1982) Immunoreactive renin and angiotensin II with hypertension due to unilateral renal artery constriction. Histochemistry 76:61–69

    Google Scholar 

  • Taugner R, Bührle CP, Hackenthal E, Mannek E, Nobiling R (1984a) Morphology of the juxtaglomerular apparatus and secretory mechanisms. Contrib Nephrol 43:76–101

    Google Scholar 

  • Taugner R, Bührle CP, Nobiling R (1984b) Ultrastructural changes associated with renin secretion from the juxtaglomerular apparatus of mice. Cell Tissue Res 237:459–472

    Google Scholar 

  • Taugner R, Bührle CP, Nobiling R, Kirschke H (1985a) Coexistence of renin and cathepsin B in epithelioid cell secretory granules. Histochemistry 83:103–108

    Google Scholar 

  • Taugner R, Whalley A, Angermüller S, Bührle CP, Hackenthal E (1985b) Are the renin-containing granules of juxtaglomerular epithelioid cells modified lyosomes? Cell Tissue Res 239:575–587

    Google Scholar 

  • Taugner R, Yokota S, Bührle CP, Hackenthal E (1986) Cathepsin D coexists with renin in the secretory granules of juxtaglomerular epithelioid cells. Histochemistry 84:19–22

    Google Scholar 

  • Taugner R, Kim SJ, Murakami K, Waldherr R (1987) The fate of prorenin during granulopoiesis in epithelioid cells. Immunocytochemical experiments with antisera against renin and different portions of the renin prosegment. Histochemistry 86:249–253

    Google Scholar 

  • Taugner R, Nobiling R, Metz R, Taugner F, Bührle C, Hackenthal E (1988) Hypothetical interpretation of the calcium paradox in renin secretion. Cell Tissue Res 252:687–690

    Google Scholar 

  • Vaitukaitis J, Robbins JB, Nischlag E, Ross GT (1971) A method for producing specific antisera with small doses of immunogen. J Clin Endocrinol 33:988–991

    Google Scholar 

  • Vander AJ, Geelhoed GW (1965) Inhibition of renin secretion by angiotensin II. Proc Soc Exp Biol Med 120:399–403

    Google Scholar 

  • Zaki FG, Keim GR, Takii Y, Inagami T (1982) Hyperplasia of juxtaglomerular cells and renin localization in kidneys of normotensive animals given captopril. Electron microscopic and immunohistochemical studies. Ann Clin Lab Sci 12:200–215

    Google Scholar 

  • Zavagali A, Aleotti A, Farinelli A (1983) Human renin granules. Ultrastructural aspects. Nephron 33:29–33

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berka, J.L.A., Alcorn, D., Ryan, G.B. et al. Renin processing studied by immunogold localization of prorenin and renin in granular juxtaglomerular cells in mice treated with enalapril. Cell Tissue Res 268, 141–148 (1992). https://doi.org/10.1007/BF00338063

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00338063

Key words

Navigation