title: Eicosanoids, mesangial contraction, and intracellular signal transduction.
abstract: 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, Kf. Cultured mesangial cells convert arachidonic acid into biologically active eicosanoids which are either contractile (thromboxane A2 [TxA2], prostaglandin F2 alpha [PGE2 alpha]) or relaxant (PGE2, PGI2). The addition of TxA2 analogues, PGE2 or sulfidopeptide leukotrienes (LTC4 and LTD4) stimulated contraction of cultured mesangial cells with threshold responses at approximately 1 nM and maximum responses at 1 microM. 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.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: P
authors.initials: P
authors.lastname: Mene'
authors.forename: M S
authors.initials: MS
authors.lastname: Simonson
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunn
mesh_terms: D000818:Animals; D015777:Eicosanoids / Q000502:physiology*; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015777:Eicosanoids