Kidney Regulation of Erythropoietin Production

  • J. W. Fisher
  • J. Nakashima
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 101)

Abstract

Hypoxia is the fundamental stimulus for erythropoietin (Ep) production (Fisher 1983, 1988; Kurz et al. 1986). Our model for kidney Ep production postulates that an oxygen deficit initiates a cascade of events which lead to increased biosynthesis and secretion of Ep. The physiologic and pathophysiologic control involved is still not clearly understood. However, there is a primary oxygen-sensing reaction in the kidney which is triggered by a reduction in ambient partial pressure of oxygen (high altitude, hypobaria); a decreased passage of oxygen across the pulmonary endothelium (obstructive lung disease); a decrease in the oxygen-carrying capacity of hemoglobin (anemia); a decrease in oxygen utilization by the kidney (cobalt) (Fisher and Birdwell 1961); and a decrease in the flow of blood to the kidney (renal artery constriction, atherosclerosis, thrombosis).

Keywords

Cobalt Lipase Superoxide Anemia NADH 

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References

  1. Beauchamp C, Fridovich I (1970) A mechanism for the production of ethylene from methional: the generation of hydroxyl radicals by xanthine oxidase. J Biol Chem 245:4641PubMedGoogle Scholar
  2. Berridge MJ (1984) Inositol triphosphate and diacylglycerol as second messengers. SOD Biochem J 222:345–360Google Scholar
  3. Daly JW (1982) Receptors: targets for future drugs. J Med Chem 25:197–207PubMedCrossRefGoogle Scholar
  4. Dionisi O, Galeotti T, Terranova T, Azzi A (1975) Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues. Biochim Biophys Acta 403:292PubMedGoogle Scholar
  5. Fink GD, Fisher JW (1977) Stimulation of erythropoiesis by beta adrenergic agonists. II. Mechanism of action. J Pharmacol Exp Ther 202:199–208PubMedGoogle Scholar
  6. Fink GD, Paulo LG, Fisher JW (1975) Effects of beta-adrenergic blocking agents on erythropoietin production in rabbits exposed to hypoxia. J Pharmacol Exp Ther 193:176–181PubMedGoogle Scholar
  7. Fisher JW (1983) Control of erythropoietin production. Proc Soc Exp Biol Med 173:289–305PubMedGoogle Scholar
  8. Fisher JW (1988) Pharmacologic modulation of erythropoietin production. Annu Rev Pharmacol Toxicol 28:101–122PubMedCrossRefGoogle Scholar
  9. Fisher JW, Birdwell BJ (1961) The production of an erythropoietin factor by the in situ perfused kidney. Acta Haematol (Basel) 26:224–232CrossRefGoogle Scholar
  10. Fisher JW (1991) Regulation of erythropoietin (Ep) production. In: Handbook of renal physiology. Oxford University Press, New York (in press)Google Scholar
  11. Goldberg MA, Glass A, Cunningham JM, Bunn HF (1987) The regulated expression of erythropoietin by two human hepatoma cell lines. Proc Natl Acad Sci USA 84:7972–7976PubMedCrossRefGoogle Scholar
  12. Guilbert LJ, Iscove NN (1976) Partial replacement of serum by selenite, transferrin, albumin and lecithin in haemopoietic cell cultures. Nature 263:594–595PubMedCrossRefGoogle Scholar
  13. Hagiwara M, Pincus SM, Chen I-L, Beckman BS, Fisher JW (1985) Effects of dibutyryl adenosine 3’-5’-cycHc monophosphate on erythropoietin production in human renal carcinoma cultues. Blood 66:714–17PubMedGoogle Scholar
  14. Hagiwara M, Nagakura K, Ueno M, Fisher JW (1987) Inhibitory effects of tetra-decanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures. Exp Cell Res 173:129–136PubMedCrossRefGoogle Scholar
  15. Huang S, Sun GY (1986) Cerebral ischemia induced quantitative changes in rat membrane lipids involved in phosphoinositide metabohsm. Neurochem Int 9:185–190PubMedCrossRefGoogle Scholar
  16. Jones DP (1986) Renal metabolism during normoxia, hypoxia, and ischemic injury. Annu Rev Physiol 48:33–50PubMedCrossRefGoogle Scholar
  17. Knowles BB, Howe CC, Aden DP (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209:497–499PubMedCrossRefGoogle Scholar
  18. Kurz AW, Jelkmann A, Pfuhl K, Malmstrom K, Bauer C (1986) Erythropoietin production by fetal mouse liver cells in response to hypoxia and adenylate cyclase. Endocrinology 118:567–572CrossRefGoogle Scholar
  19. Londos C, Wolff J (1988) Two distinct adenosine-sensitive sites on adenylate cyclase. Proc Natl Acad Sci USA 74:5482–5486CrossRefGoogle Scholar
  20. Londos C, Cooper DMF, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci USA 77:2551–2554PubMedCrossRefGoogle Scholar
  21. McCord JM (1985) Oxygen derived free radicals in postischemic tissue injury. N Engl J Med 312:159–163PubMedCrossRefGoogle Scholar
  22. Miller WL, Thomas RA, Berne RM, Rubia R (1978) Adenosine production in the ischemic kidney. Circ Res 43:390–397PubMedGoogle Scholar
  23. Nelson JA, Drake S (1984) Potentiation of methotrexate toxicity by dipyridamole. Cancer Res 44:2493–2496PubMedGoogle Scholar
  24. Nelson PK, Brookins J, Fisher JW (1983) Erythropoietin effects of prostacyclin (PGI2) and its metabolite 6-keto-prostaglandin (PGi) E. J Pharmacol Exp Ther 226:493–499PubMedGoogle Scholar
  25. Nielsen OJ, Schuster SJ, Kaufman R, Erslev AJ, Caro J (1987) Regulation of erythropoietin production in a human hepatoblastoma cell line. Blood 70: 1904–1909PubMedGoogle Scholar
  26. Osswald H, Schmitz HJ, Kemper R (1977) Tissue content of adenosine, inosine and hypoxanthine in the rat kidney after ischemia and post-ischemic recirculation. Pflugers Arch 371:45PubMedCrossRefGoogle Scholar
  27. Paul P, Rothmann SA, Meagher RC (1988) Modulation of erythropoietin production by adenosine. J Lab CHn Med 112:168–173Google Scholar
  28. Rodgers GM, Fisher JW, George WJ (1975a) Increase in hematocrit hemoglobin and red cell mass in normal mice after treatment with cyclic AMP. Proc Soc Exp Biol Med 148:380–382PubMedGoogle Scholar
  29. Rodgers GM, Fisher JW, George JW (1975b) The role of renal adenosine 3’,5’-monophosphate in the control of erythropoietin production. Am J Med 58:31PubMedCrossRefGoogle Scholar
  30. Rodgers GM, Fisher JW, George WJ (1976) Renal cyclic GMP and cholinergic mechanisms in erythropoietin production. Life Sci 17:1807–1814CrossRefGoogle Scholar
  31. Seamon KB, Padgett W, Daly JW (1981) Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci USA 78:3363–3367PubMedCrossRefGoogle Scholar
  32. Shah SV (1984) Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli. J Clin Invest 74:393–401PubMedCrossRefGoogle Scholar
  33. Sherwood JB, Burns ER, Shouval D (1987) Stimulation by cAMP of erythropoietin secretion by an established human renal carcinoma cell line. Blood 69:1053–1057PubMedGoogle Scholar
  34. Smith RJ, Fisher JW (1976) Neutral protease activity and erythropoietin production in the rat after cobalt administration. J Pharmacol Exp Ther 197:714–722PubMedGoogle Scholar
  35. Spielman WS (1984) Antagonistic effect of theophylline on the adenosine-induced decrease in renin release. Am J Physiol 247:F246-F251PubMedGoogle Scholar
  36. Strosznajder J, Wikiel H, Sun GY (1987) Effects of cerebral ischemia on [3H] inositol lipids and [3H] inositol phosphate of gerbil brain and subcellular fractions. J Neurochem 48:943–949PubMedCrossRefGoogle Scholar
  37. Toledo-Pereyra LH, Simmons RL, Najarían JS (1974) Effects of allopurinol on the preservation of ischemic kidneys perfused with plasma or plasma substitutes. Ann Surg 180:780–782PubMedCrossRefGoogle Scholar
  38. Ueno M, Brookins J, Beckman BS, Fisher JW (1988a) Effects of reactive oxygen metabolites on erythropoietin production in renal carcinoma cells. Biochem Biophys Res Commun 154:773–780PubMedCrossRefGoogle Scholar
  39. Ueno M, Brookins J, Beckman BS, Fisher JW (1988b) Effects of reactive oxygen metabolites on erythropoietin production in renal carcinoma cells. Biochem Biophys Res Commun 154:773–780PubMedCrossRefGoogle Scholar
  40. Yasuda H, Kishiro K, Izumi N, Nakanishi M (1985) Biphasic liberation of arachidonic and stearic acid during cerebral ischemia. J Neurochem 45:168–172PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • J. W. Fisher
  • J. Nakashima

There are no affiliations available

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