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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Sep;83(18):6697–6701. doi: 10.1073/pnas.83.18.6697

Extra-atrial expression of the gene for atrial natriuretic factor.

D G Gardner, C F Deschepper, W F Ganong, S Hane, J Fiddes, J D Baxter, J Lewicki
PMCID: PMC386576  PMID: 2428040

Abstract

Atrial natriuretic factor (ANF) is a group of peptides, originally isolated from the cardiac atria, that have a number of important effects on blood pressure, renal function, and salt balance. In the current study, expression of the ANF gene in certain extra-atrial tissues of the rat has been examined by radioimmunoassay of extracted ANF protein and by blot-hybridization, nuclease S1 analysis, and primer-extension analysis of the ANF mRNA. ANF peptides and mRNA were detected in cardiac ventricles, lung, and pituitary gland at levels generally less than or equal to 1% those of cardiac atria. The ANF transcripts in extra-atrial tissue appear to be very similar to those synthesized in the atria. They are polyadenylylated, are equivalent in overall length (950-1050 nucleotides), and have identical 5' termini. A secondary transcription start site mapping approximately 80 base pairs upstream from the primary start site is employed in atria and to a lesser extent in other tissues. The ANF transcript is present throughout the cardiac ventricles from apex to base and in the septum as well as the ventricular free walls. The transcript is more prevalent in the left ventricle and interventricular septum than in the right ventricle. Immunocytochemistry using various anti-rat ANF antibodies localized ANF immunoreactivity to the atrial myocytes; the ventricular myocytes, particularly along the endothelial surface of the ventricular chamber; perialveolar cells in the lung; and the gonadotropin-producing cells of the pituitary. The data indicate that the capacity for ANF gene expression extends beyond atrial tissue, albeit at much reduced levels, and may suggest alternative, perhaps paraendocrine, functions for the peptide in these tissues.

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Selected References

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  1. Ackermann U., Irizawa T. G., Milojevic S., Sonnenberg H. Cardiovascular effects of atrial extracts in anesthetized rats. Can J Physiol Pharmacol. 1984 Jul;62(7):819–826. doi: 10.1139/y84-135. [DOI] [PubMed] [Google Scholar]
  2. Argentin S., Nemer M., Drouin J., Scott G. K., Kennedy B. P., Davies P. L. The gene for rat atrial natriuretic factor. J Biol Chem. 1985 Apr 25;260(8):4568–4571. [PubMed] [Google Scholar]
  3. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  6. Currie M. G., Geller D. M., Cole B. R., Boylan J. G., YuSheng W., Holmberg S. W., Needleman P. Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. Science. 1983 Jul 1;221(4605):71–73. doi: 10.1126/science.6857267. [DOI] [PubMed] [Google Scholar]
  7. Deschepper C. F., Seidler C. D., Steele M. K., Ganong W. F. Further studies on the localization of angiotensin-II-like immunoreactivity in the anterior pituitary gland of the male rat, comparing various antisera to pituitary hormones and their specificity. Neuroendocrinology. 1985 Jun;40(6):471–475. doi: 10.1159/000124117. [DOI] [PubMed] [Google Scholar]
  8. Gutkowska J., Thibault G., Januszewicz P., Cantin M., Genest J. Direct radioimmunoassay of atrial natriuretic factor. Biochem Biophys Res Commun. 1984 Jul 31;122(2):593–601. doi: 10.1016/s0006-291x(84)80074-1. [DOI] [PubMed] [Google Scholar]
  9. Hudson P., Penschow J., Shine J., Ryan G., Niall H., Coghlan J. Hybridization histochemistry: use of recombinant DNA as a "homing probe" for tissue localization of specific mRNA populations. Endocrinology. 1981 Jan;108(1):353–356. doi: 10.1210/endo-108-1-353. [DOI] [PubMed] [Google Scholar]
  10. JAMIESON J. D., PALADE G. E. SPECIFIC GRANULES IN ATRIAL MUSCLE CELLS. J Cell Biol. 1964 Oct;23:151–172. doi: 10.1083/jcb.23.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jacobowitz D. M., Skofitsch G., Keiser H. R., Eskay R. L., Zamir N. Evidence for the existence of atrial natriuretic factor-containing neurons in the rat brain. Neuroendocrinology. 1985 Jan;40(1):92–94. doi: 10.1159/000124058. [DOI] [PubMed] [Google Scholar]
  12. Lang R. E., Thölken H., Ganten D., Luft F. C., Ruskoaho H., Unger T. Atrial natriuretic factor--a circulating hormone stimulated by volume loading. Nature. 1985 Mar 21;314(6008):264–266. doi: 10.1038/314264a0. [DOI] [PubMed] [Google Scholar]
  13. McKenzie J. C., Naruse K., Inagami T. The renin-angiotensin system in the rat anterior pituitary: colocalization of renin and angiotensin II in gonadotrophs. Anat Rec. 1985 Jun;212(2):158–166. doi: 10.1002/ar.1092120209. [DOI] [PubMed] [Google Scholar]
  14. McKenzie J. C., Tanaka I., Misono K. S., Inagami T. Immunocytochemical localization of atrial natriuretic factor in the kidney, adrenal medulla, pituitary, and atrium of rat. J Histochem Cytochem. 1985 Aug;33(8):828–832. doi: 10.1177/33.8.3160763. [DOI] [PubMed] [Google Scholar]
  15. Nakayama K., Ohkubo H., Hirose T., Inayama S., Nakanishi S. mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature. 1984 Aug 23;310(5979):699–701. doi: 10.1038/310699a0. [DOI] [PubMed] [Google Scholar]
  16. Pollock D. M., Banks R. O. Effect of atrial extract on renal function in the rat. Clin Sci (Lond) 1983 Jul;65(1):47–55. doi: 10.1042/cs0650047. [DOI] [PubMed] [Google Scholar]
  17. Saper C. B., Standaert D. G., Currie M. G., Schwartz D., Geller D. M., Needleman P. Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas. Science. 1985 Mar 1;227(4690):1047–1049. doi: 10.1126/science.2858127. [DOI] [PubMed] [Google Scholar]
  18. Tanaka I., Misono K. S., Inagami T. Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay. Biochem Biophys Res Commun. 1984 Oct 30;124(2):663–668. doi: 10.1016/0006-291x(84)91606-1. [DOI] [PubMed] [Google Scholar]
  19. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Thomas S. Reflex increase in urine flow by veratridine. Q J Exp Physiol Cogn Med Sci. 1967 Jul;52(3):313–318. doi: 10.1113/expphysiol.1967.sp001917. [DOI] [PubMed] [Google Scholar]
  21. Yamanaka M., Greenberg B., Johnson L., Seilhamer J., Brewer M., Friedemann T., Miller J., Atlas S., Laragh J., Lewicki J. Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor. Nature. 1984 Jun 21;309(5970):719–722. doi: 10.1038/309719a0. [DOI] [PubMed] [Google Scholar]
  22. Zivin R. A., Condra J. H., Dixon R. A., Seidah N. G., Chrétien M., Nemer M., Chamberland M., Drouin J. Molecular cloning and characterization of DNA sequences encoding rat and human atrial natriuretic factors. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6325–6329. doi: 10.1073/pnas.81.20.6325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Bold A. J., Borenstein H. B., Veress A. T., Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981 Jan 5;28(1):89–94. doi: 10.1016/0024-3205(81)90370-2. [DOI] [PubMed] [Google Scholar]
  24. de Bold A. J., Salerno T. A. Natriuretic activity of extracts obtained from hearts of different species and from various rat tissues. Can J Physiol Pharmacol. 1983 Feb;61(2):127–130. doi: 10.1139/y83-018. [DOI] [PubMed] [Google Scholar]
  25. de Bold A. J. Tissue fractionation studies on the relationship between an atrial natriuretic factor and specific atrial granules. Can J Physiol Pharmacol. 1982 Mar;60(3):324–330. doi: 10.1139/y82-045. [DOI] [PubMed] [Google Scholar]

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