Breyer M D, Zhang Y, Guan Y F, Hao C M, Hebert R L, Breyer R M
Department of Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee, USA.
Kidney Int Suppl. 1998 Sep;67:S88-94. doi: 10.1046/j.1523-1755.1998.06718.x.
Prostaglandin E2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein-coupled E-prostanoid receptors designated EP1-EP4. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via Gi, thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP3 receptor activation also may contribute to PGE2-mediated inhibition of NaCl absorption in the mTAL. The EP1 receptor is coupled to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE2 also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appears to be expressed both on luminal and basolateral membranes. EP4 receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.
前列腺素E2是沿肾单位产生的花生四烯酸代谢的主要环氧化酶产物。这种自分泌物质与四种不同的G蛋白偶联E-前列腺素受体相互作用，分别命名为EP1-EP4。已绘制出每种受体的肾内分布，并研究了受体激活的后果。EP3受体mRNA在髓质厚升支（mTAL）和集合管（CD）中高度表达。EP3受体激活通过Gi抑制cAMP生成，从而抑制集合管中血管加压素刺激的水重吸收。EP3受体激活也可能有助于PGE2介导的髓质厚升支中NaCl吸收的抑制。EP1受体与细胞内[Ca2+]增加有关。EP1 mRNA表达局限于集合管，受体激活抑制Na+吸收。PGE2还增加皮质厚升支和集合管中的cAMP生成；这可能是由于EP4受体激活。在集合管中很容易检测到EP4 mRNA，而几乎检测不到EP2表达。EP4受体似乎在管腔膜和基底外侧膜上均有表达。EP4受体激活也可能有助于肾小球旁器对肾素释放的调节。肾EP受体激活对盐和水平衡的影响可能取决于这些受体在肾脏中的相对表达。
