Leukotriene D4 binding and signal transduction in rat glomerular mesangial cells

K. F. Badr, S. Mong, R. L. Hoover, M. Schwartzberg, J. Ebert, H. R. Jacobson, R. C. Harris

Research output: Contribution to journalArticle

Abstract

We examined the characteristics of [3H]leukotriene D4 (LTD4) binding to mesangial cells in culture. Binding of stereoselective, specific, saturable, and rapidly reversible. Two binding sites are recognized with dissociation constants and binding site densities at equilibrium of 2.2 and 16.8 nM and 1.1 x 104 and 3 x 104 binding sites per cell. LTD4, LTE4 (5R,6S)LTD4, LTB4, and the LTD4-receptor antagonist. SKF 104353, competitively inhibit radioligand binding in the following rank order of potency: LTD4 > LTE4= SKF 104353 > (5R,6S)LTD4 > LTB4. LTD4 also induces time- and concentration-dependent phosphoinositide hydrolysis in mesangial cells. Formation of inositol 1,4,5-trisphosphate (IP3) is maximal at 5 s, followed by a time-dependent increase in inositol monophosphate generation, and inhibited by 100-fold excess concentration of SKF 104353. Addition of LTD4 to mesangial cells is associated with an increase in intracellular pH and dose-dependent stimulation of [3H]thymidine incorporation and mitogenesis. Thus rat mesangial cells possess specific binding sites for LTD4, the activation of which stimulates IP3 formation and induces cellular alkalinization and mitogenic responses. These studies provide insight into the cellular basis for LTD4-mesangial cell interactions, which are of potential pathophysiological relevance during acute glomerular inflammatory injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume257
Issue number2
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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    Badr, K. F., Mong, S., Hoover, R. L., Schwartzberg, M., Ebert, J., Jacobson, H. R., & Harris, R. C. (1989). Leukotriene D4 binding and signal transduction in rat glomerular mesangial cells. American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 257(2).