P2Y2 receptor-stimulated release of prostaglandin E2 by rat inner medullary collecting duct preparations.
P2Y2 receptor-stimulated release of prostaglandin E2 by rat inner medullary collecting duct preparations.
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P2Y2 受体刺激大鼠内髓集合管制剂释放前列腺素 E2。
DOI：
10.1152/ajprenal.00096.2003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Kishore,BellamkondaK
中科院分区：
文献类型：
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作者：
Welch,BrettD;Carlson,NoelG;Shi,Huihui;Myatt,Leslie;Kishore,BellamkondaK
细胞外核苷酸通过P2Y2受体和相关的磷脂酰肌醇-钙信号通路抑制AVP刺激的大鼠内髓集合管(IMCD)的渗透水通透性。由于细胞内钙离子的升高通常与花生四烯酸代谢增强有关，因此我们研究了P2Y2受体激活对新鲜制备的大鼠IMCD悬液中PGE2释放的影响。未刺激的IMCD释放中等但显著数量的PGE2，其对环氧合酶(COX)-2比COX-1抑制更敏感。腺苷5‘-O-(3-硫代三磷酸)激活P2Y2受体以时间和浓度依赖的方式促进PGE2从IMCD释放。非特异性COX抑制剂(氟比洛芬和2-乙酰氧基苯乙基-2-炔硫醚)可完全阻断嘌呤能刺激的PGE2释放。不同的COX抑制研究表明，嘌呤能刺激的PGE2的释放对COX-1特异性抑制剂(Valeroyl Salicylate)比COX-2特异性抑制剂(NS-398)更敏感。因此，在COX-2抑制剂存在的情况下，嘌呤能刺激导致PGE2的释放明显多于COX-1抑制剂。如果假设PGE2的释放增加与其产生的增加有关，我们的结果表明，对IMCD的嘌呤能刺激以COX-1依赖的方式导致PGE2的产生和释放增加。由于已知PGE2影响IMCD中水、盐和尿素的运输，因此IMCD中嘌呤能系统和前列腺素系统的相互作用可以调节IMCD对水、盐和尿素的处理，因此可能构成一种不依赖于AVP的调节机制。
Extracellular nucleotides, acting through the P2Y2receptor and the associated phosphoinositide-Ca2+signaling pathway, inhibit AVP-stimulated osmotic water permeability in rat inner medullary collecting duct (IMCD). Because a rise in intracellular Ca2+is frequently associated with enhanced arachidonic acid metabolism, we examined the effect of activation of the P2Y2receptor on release of PGE2in freshly prepared rat IMCD suspensions. Unstimulated IMCD released moderate, but significant, amounts of PGE2, which were more sensitive to cyclooxygenase (COX)-2 than COX-1 inhibition. Agonist activation of P2Y2receptor by adenosine 5′-O-(3-thiotriphosphate) enhanced release of PGE2from IMCD in a time- and concentration-dependent fashion. Purinergic-stimulated release of PGE2was completely blocked by nonspecific COX inhibitors (flurbiprofen and 2-acetoxyphenylhept-2-ynyl sulfide). Differential COX inhibition studies revealed that purinergic-stimulated release of PGE2was more sensitive to a COX-1-specific inhibitor (valeroyl salicylate) than a COX-2-specific inhibitor (NS-398). Thus purinergic stimulation resulted in significantly more release of PGE2in the presence of COX-2 inhibitor than COX-1 inhibitor. If it is assumed that increased release of PGE2is related to its increased production, our results suggest that purinergic stimulation of IMCD results in enhanced production and release of PGE2in a COX-1-dependent fashion. Because PGE2is known to affect transport of water, salt, and urea in IMCD, interaction of the purinergic system with the prostanoid system in IMCD can modulate handling of water, salt, and urea by IMCD and, thus, may constitute an AVP-independent regulatory mechanism.