Mene' P, Simonson M S, Dunn M J
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Tohoku J Exp Med. 1992 Jan;166(1):57-73. doi: 10.1620/tjem.166.57.
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.
肾小球系膜细胞是一种具有多种功能的特殊周细胞，包括收缩功能。系膜收缩可能会减少肾小球滤过表面积，进而降低超滤系数Kf。培养的系膜细胞可将花生四烯酸转化为具有生物活性的类二十烷酸，这些类二十烷酸要么具有收缩作用（血栓素A2 [TxA2]、前列腺素F2α [PGE2α]），要么具有舒张作用（PGE2、前列环素I2 [PGI2]）。添加TxA2类似物、PGE2或硫肽白三烯（LTC4和LTD4）可刺激培养的系膜细胞收缩，阈值反应约为1 nM，最大反应为1 μM。PGE2和PGI2可拮抗TxA2类似物诱导的系膜收缩。用非甾体抗炎药（NSAID）抑制系膜环氧化酶可增强收缩作用。具有收缩作用的类二十烷酸刺激磷脂酶C，从而提高细胞内三磷酸肌醇和胞质游离Ca2+浓度（[Ca2+]i）。具有血管舒张作用的前列腺素刺激腺苷酸环化酶，增加细胞内环磷酸腺苷（cAMP）。我们得出结论，类二十烷酸通过调节[Ca2+]i和cAMP来控制系膜收缩性。NSAID通过阻断内源性血管舒张类二十烷酸的抑制作用来增加系膜反应性，这可能会对肾小球血流动力学产生潜在影响。
