Summary
The leukotriene, LTC4, exerts a stimulatory effect on chloride transport in the frog cornea. In the work described here, the mechanism of action of LTC4 to stimulate chloride transport was studied.
In corneas pretreated with indomethacin, the effect of LTC4 was abolished, suggesting the involvement of cyclo-oxygenase products in the response. Incubation of corneas with LTC4 resulted in a significant stimulation in PGE2 synthesis, as determined by TLC-autoradiography and radioimmunoassay. In addition, LTC4 was found to stimulate cAMP synthesis in the cornea, and this stimulation was blocked with indomethacin. PGE2 was previously shown by us to be the dominant cyclo-oxygenase product formed in the frog cornea, and is capable of stimulating cAMP and chloride transport. We suggest that LTC4 stimulation of chloride transport is mediated via activation of the cyclooxygenase pathway, resulting in enhanced PGE2 synthesis. Elevated PGE2 levels induce cAMP synthesis, and ultimately, the stimulation of chloride transport. Further, the activation of cyclo-oxygenase was found to be dependent on phospholipase A2 activity. This was shown by the inhibition of the LTC4 effect in the presence of quinacrine. Similarly, inhibition of the LTC4 effect in the presence of trifluoperazine suggests that cyclo-oxygenase activation by LTC4 may be mediated via calmodulin. We have previously demonstrated that the frog cornea has the biosynthetic capacity to produce LTC4. Therefore LTC4 may function as an endogenous regulator of chloride transport in this tissue.
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References
Beitch, B.R., Beitch, I., Zadunaisky, J.A. 1974. The stimulation of chloride transport by prostaglandins and their interaction with epinephrine, theophylline, and cyclic AMP in the corneal epithelium.J. Membrane Biol. 19:381–396
Bisgaard, H., Ford-Hutchinson, A.W., Charleson, S. 1984. Production of peptido-lipid leukotrienes in human tear fluid following antigen challenge.Prostaglandins 28:620–622
Borodic, G., Conte, J., Oswad, M., Hilles, S., Robinson, D., Melvin, C., Caron, L.A., Foster, C.S. 1985. Aqueous humor leukotriene levels in animal models of inflammation.Invest. Ophthal. Vis. Sci. 26(3):99 (ARVO suppl.)
Dahlen, S.E. 1983. The significance of liberated cyclo-oxygenase products for the pulmonary and cardiovascular actions of leukotrienes C4 in the guinea-pig depends upon the route of administration.Acta Physiol. Scand. 118:415–421
Engineer, D.M., Niederhauser, U., Piper, P.J., Sirois, P. 1978. Release of mediators of anaphyloxis: Inhibition of prostaglandin synthesis and the modification of release of SRSA and histamine.Br. J. Pharmacol. 62:61–66
Guivernau, M., Terragno, A., Dunn, M.W., Terragno, N.A. 1982. Estrogens induce lipoxygenase derivative formation in rabbit lens.Invest. Ophthal. Vis. Sci. 23:214–217
Goetzl, E.J., Brindley, L.L., Goldman, D.W. 1983. Enhancement of human neutrophil adherence by synthetic leukotriene constituents of the slow-reacting substance of anaphylaxis.Immunology 50:35–41
Hammarstrom, S., Lundberg, J.M., Hera, X., Dahlen, S., Hedquist, P. 1984. Action and metabolism of circulating leukotriene C4.J. Allergy Clin. Immunol. 74:358–362
Mahlberg, K., Uusitalo, R.J., Palkama, A., Tallberg, T. 1985. Phospholipase A2 and leukotriene C4 in experimental uveitis.Invest. Ophthal. Vis. Sci. 26(3):98 (ARVO Suppl.)
Piper, P.J., Samhoun, M.N. 1981. The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea-pig, rabbit and rat.Prostaglandins 21:793–803
Reuss, L., Reinach, P., Weinman, S.A., Grady, T.P. 1983. Intracellular ion activities and Cl− transport mechanisms in bullfrog corneal epithelium.Am. J. Physiol. 244:C336-C347
Samhoun, M.N., Piper, P.J. 1984. Actions and interactions of lipoxygenase and cyclo-oxygenase products in respiratory and vascular tissues.Prostaglandins Leukotrienes Med. 13:79–87
Schaeffer, B.E., Kanchuger, M.S., Razin, M., Zadunaisky, J.A. 1982. Uptake of arachidonic acid into membrane phospholipids: Effect on chloride transport across cornea.J. Membrane Biol. 69:177–186
Schaeffer, B.E., Van Praag, D., Greenwald, L., Farber, S.J., Zadunaisky, J.A. 1984. Effects of leukotrienes on chloride transport across frog cornea.In: Prostaglandins and Membrane Ion Transport. P. Braquet, R.P. Garay, J.C. Frölich, and S. Nicosia, editors. pp. 165–172. Raven, New York
Schaeffer, B.E., Zadunaisky, J.A. 1979. Stimulation of chloride transport by fatty acids in corneal epithelium and relation to changes in membrane fluidity.Biochim. Biophys. Acta 556:131–143
Schaeffer, B.E., and Zadunaisky, J.A. 1986. Leukotriene modulation of chloride transport.Invest. Ophthal. Vis. Sci. 27:898–904
Van Praag, D., Farber, S.J. 1983. Biosynthesis of cyclooxygenase and lipoxygenase metabolites of arachidonic acid by rabbit renal microsomes.Prostaglandins Leukotrienes Med. 12:29–47
Zadunaisky, J.A. 1966. Active transport of chloride in the frog cornea.Am. J. Physiol. 211:506–512
Zadunaisky, J.A., Spring, K.R., Shindo, T. 1979. Intracellular chloride activity in the frog corneal epithelium.Fed. Proc. 38:1059
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Schaeffer, B.E., Zadunaisky, J.A. Mechanism for leukotriene C4 stimulation of chloride transport in cornea. J. Membrain Biol. 93, 229–236 (1986). https://doi.org/10.1007/BF01871177
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DOI: https://doi.org/10.1007/BF01871177