Characterization of prostanoid receptors in podocytes

Prostaglandins participate in the regulation of important glomerular functi ons and are involved in the pathogenesis of glomerular diseases. This study investigates the in prostaglandins on membrane voltage. ion conductances. cAMP accumulation, and cytosolic calcium activity ([Ca2+](i)) in differenti ated podocytes. Prostaglandin E-2 (PGE(2)) caused a concentration-dependent depolarization and an increase of the whole cell conductance in pcadocytes (EC50 approximate to 50 nM). Compared with PGE(2). the EP2/EP3/EP4 recepto r agonist 11-deoxy-PGE(1) caused an equipotent depolarization, whereas the DP receptor agonist BW 245 C, the EP1/EP3 receptor agonist sulprostone, and the IP receptor agonist iloprost were at least 100 to 1000 times less pate nt than PGE(2). The EP2 receptor agonist butaprost did not change membrane voltage of podocytes, The depolarizing effect of PGE(2) was increased in an extracellular solution with a reduced Cl; concentration (from 145 to 32 mM ), PGE(2) and the prostaglandin agonists, but not the IP receptor agonist i loprost and the EP2 receptor agonist butuprost, induced a time- and concent ration-dependent cAMP accumulation in podocytes. In fura-7 fluorescence exp eriments, PGE(2), sulprostone. PGF(2 alpha), fluprostenol (a potent FP agon ist), and U-46619 (a selective thromboxone A, agonist) induced a biphasic i ncrease of [Ca2+](i) in 60 to 80% of podocytes. In reverse transcription-PC R studies. podocyte mRNA for the EP1, EP4, FP, and TP receptor could be amp lified. These data indicate that in podocytes. PGE(2) regulates distinct ce llular functions via the EP1 and EP4 receptor, thereby increasing [Ca2+](i) , and cAMP, respectively. Furthermore, PGF(2 alpha) and U-46619 increase [C a2+](i) via their specific receptors.