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. 1997 Jan;40(1):145–150. doi: 10.1136/gut.40.1.145

Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver.

A M Vollmar 1, G Paumgartner 1, A L Gerbes 1
PMCID: PMC1027025  PMID: 9155593

Abstract

BACKGROUND: Various effects of atrial natriuretic peptide (ANP) on the liver have been observed. However, there is limited information about the types of receptors for natriuretic peptides expressed by the human liver. AIM: To investigate gene expression of the three NP receptor types (NPR) as well as of the NP in human liver. METHODS: Presence of mRNA coding for all three NPR and for ANP, brain and C-type natriuretic peptide (BNP, CNP) was investigated by reverse transcription-polymerase chain reaction (RT-PCR). Human liver tissues and hepatocellular carcinoma tissues were examined. RESULTS: Specific PCR products for all three NPR, namely NPR-A, B, and C, could be detected. Moreover, ANP and CNP, but not BNP mRNA was detectable. The concentration of ANP transcripts was up to fivefold higher in hepatocellular carcinoma compared with non-tumorous liver tissue of the same subjects. No difference in the expression of NP receptors relative to GAPDH mRNA of tumorous and non-tumorous tissue was observed except of slightly increased NPR-A transcripts. CONCLUSION: These data show that NPR transcripts are coexpressed with ANP and CNP mRNA in the human liver. This provides evidence for a local NP system in the human liver.

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  1. Bilzer M., Witthaut R., Paumgartner G., Gerbes A. L. Prevention of ischemia/reperfusion injury in the rat liver by atrial natriuretic peptide. Gastroenterology. 1994 Jan;106(1):143–151. doi: 10.1016/s0016-5085(94)94961-1. [DOI] [PubMed] [Google Scholar]
  2. Brenner B. M., Ballermann B. J., Gunning M. E., Zeidel M. L. Diverse biological actions of atrial natriuretic peptide. Physiol Rev. 1990 Jul;70(3):665–699. doi: 10.1152/physrev.1990.70.3.665. [DOI] [PubMed] [Google Scholar]
  3. Canaan-Kühl S., Jamison R. L., Myers B. D., Pratt R. E. Identification of "B" receptor for natriuretic peptide in human kidney. Endocrinology. 1992 Jan;130(1):550–552. doi: 10.1210/endo.130.1.1309350. [DOI] [PubMed] [Google Scholar]
  4. Chang M. S., Lowe D. G., Lewis M., Hellmiss R., Chen E., Goeddel D. V. Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Nature. 1989 Sep 7;341(6237):68–72. doi: 10.1038/341068a0. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Dagnino L., Lavigne J. P., Nemer M. Increased transcripts for B-type natriuretic peptide in spontaneously hypertensive rats. Quantitative polymerase chain reaction for atrial and brain natriuretic peptide transcripts. Hypertension. 1992 Nov;20(5):690–700. doi: 10.1161/01.hyp.20.5.690. [DOI] [PubMed] [Google Scholar]
  7. Gerbes A. L., Dagnino L., Nguyen T., Nemer M. Transcription of brain natriuretic peptide and atrial natriuretic peptide genes in human tissues. J Clin Endocrinol Metab. 1994 Jun;78(6):1307–1311. doi: 10.1210/jcem.78.6.8200930. [DOI] [PubMed] [Google Scholar]
  8. Gerbes A. L., Nemer M. Detection of C-type natriuretic peptide compared with brain and atrial natriuretic peptide transcripts in human heart by the polymerase chain reaction. Clin Investig. 1993 Aug;71(8):672–672. doi: 10.1007/BF00184500. [DOI] [PubMed] [Google Scholar]
  9. Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gutkowska J., Nemer M. Structure, expression, and function of atrial natriuretic factor in extraatrial tissues. Endocr Rev. 1989 Nov;10(4):519–536. doi: 10.1210/edrv-10-4-519. [DOI] [PubMed] [Google Scholar]
  11. Hagiwara H., Sakaguchi H., Itakura M., Yoshimoto T., Furuya M., Tanaka S., Hirose S. Autocrine regulation of rat chondrocyte proliferation by natriuretic peptide C and its receptor, natriuretic peptide receptor-B. J Biol Chem. 1994 Apr 8;269(14):10729–10733. [PubMed] [Google Scholar]
  12. Itoh H., Pratt R. E., Ohno M., Dzau V. J. Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells. Hypertension. 1992 Jun;19(6 Pt 2):758–761. doi: 10.1161/01.hyp.19.6.758. [DOI] [PubMed] [Google Scholar]
  13. Koller K. J., Lowe D. G., Bennett G. L., Minamino N., Kangawa K., Matsuo H., Goeddel D. V. Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). Science. 1991 Apr 5;252(5002):120–123. doi: 10.1126/science.1672777. [DOI] [PubMed] [Google Scholar]
  14. Lowe D. G., Chang M. S., Hellmiss R., Chen E., Singh S., Garbers D. L., Goeddel D. V. Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction. EMBO J. 1989 May;8(5):1377–1384. doi: 10.1002/j.1460-2075.1989.tb03518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nair B. G., Steinke L., Yu Y. M., Rashed H. M., Seyer J. M., Patel T. B. Increase in the number of atrial natriuretic hormone receptors in regenerating rat liver. J Biol Chem. 1991 Jan 5;266(1):567–573. [PubMed] [Google Scholar]
  16. Nakao K., Ogawa Y., Suga S., Imura H. Molecular biology and biochemistry of the natriuretic peptide system. II: Natriuretic peptide receptors. J Hypertens. 1992 Oct;10(10):1111–1114. doi: 10.1097/00004872-199210000-00002. [DOI] [PubMed] [Google Scholar]
  17. Nemer M., Chamberland M., Sirois D., Argentin S., Drouin J., Dixon R. A., Zivin R. A., Condra J. H. Gene structure of human cardiac hormone precursor, pronatriodilatin. Nature. 1984 Dec 13;312(5995):654–656. doi: 10.1038/312654a0. [DOI] [PubMed] [Google Scholar]
  18. Nunez D. J., Dickson M. C., Brown M. J. Natriuretic peptide receptor mRNAs in the rat and human heart. J Clin Invest. 1992 Nov;90(5):1966–1971. doi: 10.1172/JCI116075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pella R. The protective effect of atrial natriuretic peptide (ANP) on cells damaged by oxygen radicals is mediated through elevated CGMP-levels, reduction of calcium-inflow and probably G-proteins. Biochem Biophys Res Commun. 1991 Jan 31;174(2):549–555. doi: 10.1016/0006-291x(91)91452-i. [DOI] [PubMed] [Google Scholar]
  20. Porter J. G., Arfsten A., Fuller F., Miller J. A., Gregory L. C., Lewicki J. A. Isolation and functional expression of the human atrial natriuretic peptide clearance receptor cDNA. Biochem Biophys Res Commun. 1990 Sep 14;171(2):796–803. doi: 10.1016/0006-291x(90)91216-f. [DOI] [PubMed] [Google Scholar]
  21. Rashed H. M., Sun H., Patel T. B. Atrial natriuretic peptide inhibits growth of hepatoblastoma (HEP G2) cells by means of activation of clearance receptors. Hepatology. 1993 Apr;17(4):677–684. doi: 10.1002/hep.1840170423. [DOI] [PubMed] [Google Scholar]
  22. Rosenzweig A., Seidman C. E. Atrial natriuretic factor and related peptide hormones. Annu Rev Biochem. 1991;60:229–255. doi: 10.1146/annurev.bi.60.070191.001305. [DOI] [PubMed] [Google Scholar]
  23. Samson W. K., Skala K. D., Huang F. L. CNP-22 stimulates, rather than inhibits, water drinking in the rat: evidence for a unique biological action of the C-type natriuretic peptides. Brain Res. 1991 Dec 24;568(1-2):285–288. doi: 10.1016/0006-8993(91)91410-3. [DOI] [PubMed] [Google Scholar]
  24. Seilhamer J. J., Arfsten A., Miller J. A., Lundquist P., Scarborough R. M., Lewicki J. A., Porter J. G. Human and canine gene homologs of porcine brain natriuretic peptide. Biochem Biophys Res Commun. 1989 Dec 15;165(2):650–658. doi: 10.1016/s0006-291x(89)80015-4. [DOI] [PubMed] [Google Scholar]
  25. Stingo A. J., Clavell A. L., Aarhus L. L., Burnett J. C., Jr Cardiovascular and renal actions of C-type natriuretic peptide. Am J Physiol. 1992 Jan;262(1 Pt 2):H308–H312. doi: 10.1152/ajpheart.1992.262.1.H308. [DOI] [PubMed] [Google Scholar]
  26. Sudoh T., Kangawa K., Minamino N., Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988 Mar 3;332(6159):78–81. doi: 10.1038/332078a0. [DOI] [PubMed] [Google Scholar]
  27. Sudoh T., Minamino N., Kangawa K., Matsuo H. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990 Apr 30;168(2):863–870. doi: 10.1016/0006-291x(90)92401-k. [DOI] [PubMed] [Google Scholar]
  28. Tawaragi Y., Fuchimura K., Tanaka S., Minamino N., Kangawa K., Matsuo H. Gene and precursor structures of human C-type natriuretic peptide. Biochem Biophys Res Commun. 1991 Mar 15;175(2):645–651. doi: 10.1016/0006-291x(91)91614-i. [DOI] [PubMed] [Google Scholar]
  29. Terada Y., Tomita K., Nonoguchi H., Yang T., Marumo F. PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments. Am J Physiol. 1994 Aug;267(2 Pt 2):F215–F222. doi: 10.1152/ajprenal.1994.267.2.F215. [DOI] [PubMed] [Google Scholar]
  30. Tremblay J., Huot C., Willenbrock R. C., Bayard F., Gossard F., Fujio N., Koch C., Kuchel O., Debinski W., Hamet P. Increased cyclic guanosine monophosphate production and overexpression of atrial natriuretic peptide A-receptor mRNA in spontaneously hypertensive rats. J Clin Invest. 1993 Nov;92(5):2499–2508. doi: 10.1172/JCI116858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vollmar A. M., Gerbes A. L., Nemer M., Schulz R. Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs. Endocrinology. 1993 Apr;132(4):1872–1874. doi: 10.1210/endo.132.4.8462485. [DOI] [PubMed] [Google Scholar]
  33. Vollmar A. M., Schulz R. Expression and differential regulation of natriuretic peptides in mouse macrophages. J Clin Invest. 1995 Jun;95(6):2442–2450. doi: 10.1172/JCI117944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vollmar A. M., Schulz R. Gene expression and secretion of atrial natriuretic peptide by murine macrophages. J Clin Invest. 1994 Aug;94(2):539–545. doi: 10.1172/JCI117367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vollmar A. M., Wolf R., Schulz R. Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus. J Neuroimmunol. 1995 Mar;57(1-2):117–127. doi: 10.1016/0165-5728(94)00171-j. [DOI] [PubMed] [Google Scholar]
  36. Waldman S. A., Lewicki J. A., Brandwein H. J., Murad F. Partial purification and characterization of particulate guanylate cyclase from rat liver after solubilization with trypsin. J Cyclic Nucleotide Res. 1982;8(6):359–370. [PubMed] [Google Scholar]
  37. Wei C. M., Heublein D. M., Perrella M. A., Lerman A., Rodeheffer R. J., McGregor C. G., Edwards W. D., Schaff H. V., Burnett J. C., Jr Natriuretic peptide system in human heart failure. Circulation. 1993 Sep;88(3):1004–1009. doi: 10.1161/01.cir.88.3.1004. [DOI] [PubMed] [Google Scholar]
  38. Wilcox J. N., Augustine A., Goeddel D. V., Lowe D. G. Differential regional expression of three natriuretic peptide receptor genes within primate tissues. Mol Cell Biol. 1991 Jul;11(7):3454–3462. doi: 10.1128/mcb.11.7.3454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. von Ruecker A. A., Wild M., Rao G. S., Bidlingmaier F. Atrial natriuretic peptide protects hepatocytes against damage induced by hypoxia and reactive oxygen. Possible role of intracellular free ionized calcium. J Clin Chem Clin Biochem. 1989 Sep;27(9):531–537. doi: 10.1515/cclm.1989.27.9.531. [DOI] [PubMed] [Google Scholar]

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