Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Aug;92(2):858–865. doi: 10.1172/JCI116660

Na+/H+ exchange in human lymphocytes and platelets in chronic and subacute metabolic acidosis.

H P Reusch 1, R Reusch 1, D Rosskopf 1, W Siffert 1, J F Mann 1, F C Luft 1
PMCID: PMC294924  PMID: 8394388

Abstract

The effect of acid-base disturbances on sodium/proton (Na+/H+) exchange has been examined in animal models; however, few data are available from human studies. To test the effect of metabolic acidosis on Na+/H+ exchange in man, as well as to examine the relationship between Na+/H+ exchange and cytosolic calcium ([Ca2+]i), we measured both variables in patients with decreased renal function with mild metabolic acidosis (pH 7.34 +/- 0.06), in normal control subjects (pH 7.41 +/- 0.02), and in subjects before (pH 7.40 +/- 0.01), and after (pH 7.26 +/- 0.04) ammonium chloride (NH4Cl) 15 g for 5 d. Lymphocytes and platelets were loaded with the cytosolic pH (pHi) indicator 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein and acidified to pH approximately 6.6 with propionic acid. To quantitate Na+/H+ exchange, dpHi/dt was determined at 1 min. [Ca2+]i was measured with fura-2. Na+/H+ exchange was significantly increased only in lymphocytes of patients with renal insufficiency. Neither intracellular pH (pHi) nor [Ca2+]i was different from controls. NH4Cl resulted in a significant increase in Na+/H+ exchange in lymphocytes, but not in platelets of normal subjects. Values of pHi and [Ca2+]i in either cell type remained unaffected. Since metabolic acidosis influenced Na+/H+ only in lymphocytes, but not in platelets, it is possible that protein synthesis may be involved in increasing Na+/H+ exchange.

Full text

PDF
862

Selected References

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

  1. Davis J. O., Freeman R. H. Mechanisms regulating renin release. Physiol Rev. 1976 Jan;56(1):1–56. doi: 10.1152/physrev.1976.56.1.1. [DOI] [PubMed] [Google Scholar]
  2. Forster H. V., Dempsey J. A., Thomson J., Vidruk E., DoPico G. A. Estimation of arterial PO2, PCO2, pH, and lactate from arterialized venous blood. J Appl Physiol. 1972 Jan;32(1):134–137. doi: 10.1152/jappl.1972.32.1.134. [DOI] [PubMed] [Google Scholar]
  3. Grinstein S., Rothstein A. Mechanisms of regulation of the Na+/H+ exchanger. J Membr Biol. 1986;90(1):1–12. doi: 10.1007/BF01869680. [DOI] [PubMed] [Google Scholar]
  4. Grinstein S., Rotin D., Mason M. J. Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta. 1989 Jan 18;988(1):73–97. doi: 10.1016/0304-4157(89)90004-x. [DOI] [PubMed] [Google Scholar]
  5. Haggerty J. G., Agarwal N., Reilly R. F., Adelberg E. A., Slayman C. W. Pharmacologically different Na/H antiporters on the apical and basolateral surfaces of cultured porcine kidney cells (LLC-PK1). Proc Natl Acad Sci U S A. 1988 Sep;85(18):6797–6801. doi: 10.1073/pnas.85.18.6797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Haynes A. P., Daniels I., Porter C., Fletcher J., Morgan A. G. Abnormal cytoplasmic pH regulation during activation in uremic neutrophils. Kidney Int. 1992 Sep;42(3):690–699. doi: 10.1038/ki.1992.336. [DOI] [PubMed] [Google Scholar]
  7. Horie S., Moe O., Yamaji Y., Cano A., Miller R. T., Alpern R. J. Role of protein kinase C and transcription factor AP-1 in the acid-induced increase in Na/H antiporter activity. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5236–5240. doi: 10.1073/pnas.89.12.5236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Huot S. J., Aronson P. S. Na(+)-H+ exchanger and its role in essential hypertension and diabetes mellitus. Diabetes Care. 1991 Jun;14(6):521–535. doi: 10.2337/diacare.14.6.521. [DOI] [PubMed] [Google Scholar]
  9. Kotchen T. A., Welch W. J., Lorenz J. N., Ott C. E. Renal tubular chloride and renin release. J Lab Clin Med. 1987 Nov;110(5):533–540. [PubMed] [Google Scholar]
  10. Krapf R., Beeler I., Hertner D., Hulter H. N. Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med. 1991 May 16;324(20):1394–1401. doi: 10.1056/NEJM199105163242003. [DOI] [PubMed] [Google Scholar]
  11. Krapf R., Pearce D., Lynch C., Xi X. P., Reudelhuber T. L., Pouysségur J., Rector F. C., Jr Expression of rat renal Na/H antiporter mRNA levels in response to respiratory and metabolic acidosis. J Clin Invest. 1991 Feb;87(2):747–751. doi: 10.1172/JCI115057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moe O. W., Miller R. T., Horie S., Cano A., Preisig P. A., Alpern R. J. Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts. J Clin Invest. 1991 Nov;88(5):1703–1708. doi: 10.1172/JCI115487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Perper R. J., Zee T. W., Mickelson M. M. Purification of lymphocytes and platelets by gradient centrifugation. J Lab Clin Med. 1968 Nov;72(5):842–848. [PubMed] [Google Scholar]
  14. Poli de Figueiredo C. E., Ng L. L., Garrido M. C., Davies J. E., Ellory J. C., Hendry B. M. Leukocyte intracellular pH and Na/H antiporter activity in uraemia and type I diabetes mellitus. Nephrol Dial Transplant. 1991;6(9):615–620. doi: 10.1093/ndt/6.9.615. [DOI] [PubMed] [Google Scholar]
  15. Pollock W. K., Rink T. J., Irvine R. F. Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura-2-loaded human platelets stimulated by ionomycin and collagen. Biochem J. 1986 May 1;235(3):869–877. doi: 10.1042/bj2350869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. RELMAN A. S., SHELBURNE P. F., TALMAN A. Profound acidosis resulting from excessive ammonium chloride in previously healthy subjects. A study of two cases. N Engl J Med. 1961 Apr 27;264:848–852. doi: 10.1056/NEJM196104272641703. [DOI] [PubMed] [Google Scholar]
  17. Rosskopf D., Siffert G., Osswald U., Witte K., Düsing R., Akkerman J. W., Siffert W. Platelet Na(+)-H+ exchanger activity in normotensive and hypertensive subjects: effect of enalapril therapy upon antiport activity. J Hypertens. 1992 Aug;10(8):839–847. [PubMed] [Google Scholar]
  18. Siffert W., Siffert G., Scheid P. Activation of Na+/H+ exchange in human platelets stimulated by thrombin and a phorbol ester. Biochem J. 1987 Jan 1;241(1):301–303. doi: 10.1042/bj2410301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Siffert W., Siffert G., Scheid P., Akkerman J. W. Na+/H+ exchange modulates Ca2+ mobilization in human platelets stimulated by ADP and the thromboxane mimetic U 46619. J Biol Chem. 1990 Jan 15;265(2):719–725. [PubMed] [Google Scholar]
  20. Simpson F. O. Sodium intake, body sodium, and sodium excretion. Lancet. 1988 Jul 2;2(8601):25–29. doi: 10.1016/s0140-6736(88)92954-6. [DOI] [PubMed] [Google Scholar]
  21. Strazzullo P., Canessa M. Kinetics of the human lymphocyte Na(+)-H+ exchanger. Clin Sci (Lond) 1990 Nov;79(5):531–536. doi: 10.1042/cs0790531. [DOI] [PubMed] [Google Scholar]
  22. Weinberger M. H., Ramsdell J. W., Rosner D. R., Geddes J. J. Effect of chlorothiazide and sodium on vascular responsiveness to angiotensin II. Am J Physiol. 1972 Nov;223(5):1049–1052. doi: 10.1152/ajplegacy.1972.223.5.1049. [DOI] [PubMed] [Google Scholar]

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

RESOURCES