Eicosanoids, Mesangial Contraction, and Intracellular Signal Transduction

Abstract

Nephrology, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA MENE', P., SIMONSON, M.S. and DUNN, M.J. Eicosanoids, Mesangial Contraction, and Intracellular Signal Transduction. Tohoku J. Exp. Med., 1992, 166 (1), 57-73-The glomerular mesangial cell is a specialized pericyte with multiple functional capabilities including contraction. Mesangial contraction may reduce the glomerular filtration surface area and hence the ultrafiltration coefficient, K_f. Cultured mesangial cells convert arachidonic acid into biologically active eicosanoids which are either contractile (thromboxane A₂ [TxA₂], prostaglandin F_2α [PGE_2α]) or relaxant (POE₂, PGI₂). The addition of TxA₂ analogues, PGE₂ or sulfidopeptide leukotrienes (LTC₄ and LTD₄) stimulated contraction of cultured mesangial cells with threshold responses at approximately 1nM and maximum responses at 1μM. PGE₂ and PGI₂ antagonized mesangial contraction induced by TxA₂ analogues. Contraction was enhanced by inhibiting mesangial cyclooxygenase with nonsteroidal antiinflammatory drugs (NSAID). Contractile eicosanoids stimulated phospholipase C thereby elevating intracellular inositol trisphosphate and cytosolic free Ca²⁺ concentration ([Ca²⁺]_i). Vasorelaxant prostanoids stimulated adenylate cyclase, increasing intracellular cyclic AMP. We conclude that eicosanoids control mesangial contractility by regulating [Ca²⁺]_i and CAMP. NSAID increase mesangial reactivity by blocking the inhibitory effects of endogenous vasodilator eicosanoids, with potential consequences on glomerular hemodynamics.