Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Dec;58(6):1370–1378. doi: 10.1172/JCI108592

Modulation of the cyclic AMP content of rat renal inner medulla by oxygen: possible role of local prostaglandins.

F R DeRubertis, T V Zenser, P A Craven, B B Davis
PMCID: PMC333308  PMID: 186490

Abstract

The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins.

Full text

PDF
1370

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. APERIA A. C., LIEBOW A. A. IMPLICATIONS OF URINE PO2 FOR RENAL MEDULLARY BLOOD FLOW. Am J Physiol. 1964 Mar;206:499–504. doi: 10.1152/ajplegacy.1964.206.3.499. [DOI] [PubMed] [Google Scholar]
  2. Anggård E., Bohman S. O., Griffin J. E., 3rd, Larsson C., Maunsbach A. B. Subcellular localization of the prostaglandin system in the rabbit renal papilla. Acta Physiol Scand. 1972 Feb;84(2):231–246. doi: 10.1111/j.1748-1716.1972.tb05174.x. [DOI] [PubMed] [Google Scholar]
  3. BERNANKE D., EPSTEIN F. H. METABOLISM OF THE RENAL MEDULLA. Am J Physiol. 1965 Mar;208:541–545. doi: 10.1152/ajplegacy.1965.208.3.541. [DOI] [PubMed] [Google Scholar]
  4. Beck N. P., Kaneko T., Zor U., Field J. B., Davis B. B. Effects of vasopressin and prostaglandin E 1 on the adenyl cyclase-cyclic 3',5'-adenosine monophosphate system of the renal medulla of the rat. J Clin Invest. 1971 Dec;50(12):2461–2465. doi: 10.1172/JCI106746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beck N. P., Reed S. W., Murdaugh H. V., Davis B. B. Effects of catecholamines and their interaction with other hormones on cyclic 3',5'-adenosine monophosphate of the kidney. J Clin Invest. 1972 Apr;51(4):939–944. doi: 10.1172/JCI106888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boudreau R. J., Drummond G. I. A modified assay of 3':5'-cyclic-AMP phosphodiesterase. Anal Biochem. 1975 Feb;63(2):388–399. doi: 10.1016/0003-2697(75)90361-9. [DOI] [PubMed] [Google Scholar]
  7. Crowshaw K. The incorporation of (1-14C) arachidonic acid into the lipids of rabbit renal slices and conversion to prostaglandins E2 and F2 . Prostaglandins. 1973 May;3(5):607–620. doi: 10.1016/0090-6980(73)90098-1. [DOI] [PubMed] [Google Scholar]
  8. DeRubertis F. R., Craven P. Effects of reduced ATP concent on hepatic responses to glucagon. Metabolism. 1976 Jan;25(1):57–67. doi: 10.1016/0026-0495(76)90160-8. [DOI] [PubMed] [Google Scholar]
  9. DeRubertis F. R., Craven P. Reduced sensitivity of the hepatic adenylate cyclase-cyclic AMP system to glucagon during sustained hormonal stimulation. J Clin Invest. 1976 Feb;57(2):435–443. doi: 10.1172/JCI108294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eckenfels A., Vane J. R. Prostaglandins, oxygen tension and smooth muscle tone. Br J Pharmacol. 1972 Jul;45(3):451–462. doi: 10.1111/j.1476-5381.1972.tb08101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Flores A. G., Sharp G. W. Endogenous prostaglandins and osmotic water flow in the toad bladder. Am J Physiol. 1972 Dec;223(6):1392–1397. doi: 10.1152/ajplegacy.1972.223.6.1392. [DOI] [PubMed] [Google Scholar]
  12. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  13. Frolich J. C., Sweetman B. J., Carr K., Oates J. A. Prostaglandin synthesis in rabbit renal medulla. Life Sci. 1975 Oct 10;17(7):1105–1111. doi: 10.1016/0024-3205(75)90331-8. [DOI] [PubMed] [Google Scholar]
  14. Hamberg M. Biosynthesis of prostaglandins in the renal medulla of rabbit. FEBS Lett. 1969 Oct 21;5(2):127–130. doi: 10.1016/0014-5793(69)80312-1. [DOI] [PubMed] [Google Scholar]
  15. KEAN E. L., ADAMS P. H., DAVIES H. C., WINTERS R. W., DAVIES R. E. Oxygen consumption and respiratory pigments of mitochondria of the inner medulla of the dog kidney. Biochim Biophys Acta. 1962 Nov 5;64:503–507. doi: 10.1016/0006-3002(62)90308-6. [DOI] [PubMed] [Google Scholar]
  16. KEAN E. L., ADAMS P. H., WINTERS R. W., DAVIES R. E. Energy metabolism of the renal medulla. Biochim Biophys Acta. 1961 Dec 23;54:474–478. doi: 10.1016/0006-3002(61)90087-7. [DOI] [PubMed] [Google Scholar]
  17. KRAMER K., THURAU K., DEETJEN P. [Hemodynamics of kidney medullary substance. Part I. Capillary passage time, blood volume, circulation, tissue hematocrit and oxygen consumption of kidney medullary substance in situ]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:251–269. [PubMed] [Google Scholar]
  18. LEE J. B., VANCE V. K., CAHILL G. F., Jr Metabolism of C14-labeled substrates by rabbit kidney cortex and medulla. Am J Physiol. 1962 Jul;203:27–36. doi: 10.1152/ajplegacy.1962.203.1.27. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Levitt M. J., Tobon H., Josimovich J. B. Prostaglandin content of human endometrium. Fertil Steril. 1975 Mar;26(3):296–300. doi: 10.1016/s0015-0282(16)41000-9. [DOI] [PubMed] [Google Scholar]
  21. RENNIE D. W., REEVES R. B., PAPPENHEIMER J. R. Oxygen pressure in urine and its relation to intrarenal blood flow. Am J Physiol. 1958 Oct;195(1):120–132. doi: 10.1152/ajplegacy.1958.195.1.120. [DOI] [PubMed] [Google Scholar]
  22. RHODIN J. Electron microscopy of the kidney. Am J Med. 1958 May;24(5):661–675. doi: 10.1016/0002-9343(58)90373-5. [DOI] [PubMed] [Google Scholar]
  23. STERNBERG W. H., FARBER E., DUNLAP C. E. Histochemical localization of specific oxidative enzymes. II. Localization of diphosphopyridine nucleotide and triphosphopyridine nucleotide diaphorases and the succindehydrogenase system in the kidney. J Histochem Cytochem. 1956 May;4(3):266–283. doi: 10.1177/4.3.266. [DOI] [PubMed] [Google Scholar]
  24. Thompson W. J., Appleman M. M. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Biochemistry. 1971 Jan 19;10(2):311–316. [PubMed] [Google Scholar]
  25. WHITEHOUSE M. W., HASLAM J. M. Ability of some antirheumatic drugs to uncouple oxidative phosphorylation. Nature. 1962 Dec 29;196:1323–1324. doi: 10.1038/1961323a0. [DOI] [PubMed] [Google Scholar]
  26. Zins G. R. Renal prostaglandins. Am J Med. 1975 Jan;58(1):14–24. doi: 10.1016/0002-9343(75)90528-8. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES