Summary
PGE2 and LTC4 syntheses in Ehrlich ascites cells were measured by radioimmunoassay. Hypotonic swelling results in stimulation of the leukotriene synthesis and a concomitant reduction in the prostaglandin synthesis. If the cells have access to sufficient arachidonic acid there is a parallel increase in the synthesis of both leukotrienes and prostaglandins following hypotonic exposure. PGE2 significantly inhibits regulatory volume decrease (RVD) following hypotonic swelling in Na-containing medium but not in Na-free media, supporting the hypothesis that the effect of PGE2 is on the Na permeability. PGE2 also had no effect on RVD in Na-free media in the presence of the cation ionophore gramicidin. Since the Cl permeability becomes rate limiting for RVD in the presence of gramicidin, whereas the K permeability is rate limiting in its absence, it is concluded that PGE2 neither affects Cl nor K permeability. Addition of LTD4 accelerates RVD and since the K permeability is rate limiting for RVD this shows that LTD4 stimulates the K permeability. Inhibition of the leukotriene synthesis by nordihydroguaiaretic acid inhibits RVD even when a high K conductance has been ensured by the presence of gramicidin. It is, therefore, proposed that an increase in leukotriene synthesis after hypotonic swelling is involved also in the activation of the Cl transport pathway.
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References
Berridge, M.J. 1982. A novel cellular signaling system based on the integration of phospholipids and calcium metabolism.In: Calcium and Cell Function. Vol III, pp. 1–36. W.Y. Cheung, editor. Academic, New York
Berridge, M.J. 1984. Inositol trisphosphate and diacylglycerol as second messengers.Biochem. J. 220:345–360
Blackstock, E.J., Ellory, J.C., Stewart, G.W. 1985. N-methyl-d-glucamine as a cation replacement for human red-cell transport studies.J. Physiol. (London) 358:90P
Braquet, M., Chereau, A., Chabrier, E., Braquet, P. 1984. The membrane signal in human leukocyte: Evidence for a calcium-dependent potassium permeability in a A23187-induced-triggering for arachidonate cascade.Biomed. Biochim. Acta 43:366–372
Brune, K., Peskar, B.A. 1985. Modulation by drugs of leukotriene and prostaglandin production from mouse peritoneal macrophages.Int. J. Tiss. Reac. VII:97–103
Cashman, J.R. 1985. Leukotriene biosynthesis inhibitors.Pharmaceut. Res. 6:253–261
Christensen, P., Gréen, K., Leyssac, P.P. 1983. The relationship between urinary prostaglandin excretion rates and flow in conscious rats. Evaluation of the radioimmunoassay by gas chromatography-mass spectrometry.Acta Physiol. Scand. 117:41–47
Christensen, P., Leyssac, P.P. 1976. A specific radioimmunoassay for PGE2 using an antibody with high specificity and a sephadex LH-20 microculumn for the separation of prostaglandins.Prostaglandins 11:399–420
Craven, P.A., DeRubertis, F.R. 1983. Ca2+ calmodulin-dependent release of arachidonic acid for renal medullary prostaglandin synthesis.J. Biol. Chem. 258:4814–4823
Dembinska-Kiec, A., Korbut, R., Zmuda, A., Kostka-Trabka, E., Simmet, T., Peskar, B.A. 1984. Formation of lipoxygenase and cyclooxygenase metabolites of arachidonic acid by brain tissue.Biomed. Biochim. Acta 43:222–226
Erlij, D., Gersten, L., Sterba, G. 1981. Calcium prostaglandin and transepithelial sodium transport.J. Physiol. (London) 320:136P
Feinstein, M.B., Sha'afi R.I. 1983. Role of calcium in arachidonic acid metabolism and in the actions of arachidonic acidderived metabolites.Calcium Cell Function IV:337–376
Grinstein, S., Clarke, C.A., Dupre, A., Rothstein, A. 1982. Volume-induced increase of anion permeability in human lymphocytes.J. Gen. Physiol. 80:801–823
Hall, W.J., O'Donogue, J.P., O'Regan, M.G., Penny, W.J. 1976. Endogenous prostaglandins, adenosine 3′∶5′-monophosphate and sodium transport across isolated frog skin.J. Physiol. (London) 258:731–753
Hammerström, S., Ørning, L., Bernström, K. 1985. Metabolism of leukotrienes.Mol. Cell. Biochem. 69:7–16
Hansen, H.S. 1983. Dietary essential fatty acids and in vivo prostaglandin production in mammals.Wld. Rev. Nutr. Diet. 42:102–134
Hoffmann, E.K. 1978. Regulation of cell volume by selective changes in the leak permeabilities of Ehrlich ascites tumor cells:In. Osmotic and Volume Regulation. Alfred Benzon Symposium XI. C.B. Jørgensen and E. Skadhauge, editors. pp. 397–417 Munksgaard, Copenhagen
Hoffmann, E.K., Lambert, I.H., Simonsen, L.O. 1984a. Separate K and Cl transport pathways activated by Ca in Ehrlich mouse ascites tumor cells.J. Physiol (London) 357:62P
Hoffmann, E.K., Lambert, I.H., Simonsen, L.O. 1986. Separate, Ca2+-activated K+ and Cl− transport pathways in Ehrlich ascites tumor cells.J. Membrane Biol. 91:227–244
Hoffmann, E.K., Simonsen, L.O., Lambert, I.H. 1984b. Volume-induced increase of K+ and Cl− permeabilities in Ehrlich ascites tumor cells. Role of internal Ca2+.J. Membrane Biol. 78:211–222
Hoffmann, E.K., Simonsen, L.O., Sjöholm, C. 1979. Membrane potential, chloride exchange, and chloride conductance in Ehrlich mouse ascites tumour cells.J. Physiol. (London) 296:61–84
Irvine, R.F. 1982. How is the level of free arachidonic acid controlled in mammals?Biochem. J. 204:3–16
Lambert, I.H. 1987. Effect of arachidonic acid, fatty acids, prostaglandins and leukotrienes on volume regulation in Ehrlich ascites tumor cells.J. Membrane Biol. 98:207–221
Lambert, I.H., Hoffmann, E.K. 1982. Amino acid metabolism and protein turnover under different osmotic conditions in Ehrlich ascites tumor cells.Mol. Physiol. 2:273–286
Lambert, I.H., Hoffmann, E.K., Christensen, P. 1986. Prostaglandin and leukotriene release during volume regulation in Ehrlich ascites cells.Acta Physiol. Scand. 128:P56
Leikauf, G.D., Ueki, I.F., Widdicombe, J.H., Nadel, J.A., 1986. Alteration of chloride secretion across canine tracheal epithelium by lipoxygenase products of arachidonic acid.Am. J. Physiol. 250:F47-F53
Leyssac, P.P., Christensen, P. 1981. A study of the effect of stimulated endogenous prostaglandin synthesis on urine flow, osmolar excretion rate, and renin release in hydropenic and saline loaded, anesthetized rats.Acta Physiol. Scand. 113:23–31
Needleman, P., Turk, J., Jakschik, B.A., Morrison, A.R., Lefkowith, J.B. 1986. Arachidonic acid metabolism.Annu. Rev. Biochem. 55:69–102
Nielsen, R., Bjerregaard, H.F. 1984. Intracellular Ca and prostaglandin as regulator of active Na-transport in frog skin. First Int. Congr. Comp. Physiol. Biochem. 88, B 88. Liege, Belgium.
Rouzer, C.A., Samuelsson, B. 1985. On the nature of the 5-lipoxygenase reaction in human leukocytes: Enzyme purification and requirement for multiple stimulatory factors.Proc. Natl. Acad. Sci USA 82:6040–6044
Samuelsson, B. 1983. Leukotrienes: Mediators of immediate hypersensitivity reactions and inflammation.Science 220:568–575
Schaeffer, B.E., Zadunaisky, J.A. 1986. Mechanism for leukotriene-C4 stimulation of chloride transport in cornea.J. Membrane Biol. 93:229–236
Schulz, R., Seeger, W. 1986. Release of leukotrienes into the perfusate of calcium-ionophore stimulated rabbit lungs.Biochem. Pharmacol. 35:183–193
Sullivan, M.H.F., Cooke, B.A. 1985. Control and production of leukotriene B4 in rat tumour and testicular Leydig cells.Biochem. J. 230:821–824
Van den Bosch, H. 1980. Intracellular phospholipase A.Biochim. Biophys. Acta 604:191–246
Wong, P.Y.K., Cheung, W.Y. 1979. Calmodulin stimulates human platelet phospholipase A2.Biochem. Biophys. Res. Commun. 90:473–480
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Lambert, I.H., Hoffmann, E.K. & Christensen, P. Role of prostaglandins and leukotrienes in volume regulation by Ehrlich ascites tumor cells. J. Membrain Biol. 98, 247–256 (1987). https://doi.org/10.1007/BF01871187
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DOI: https://doi.org/10.1007/BF01871187