Recent studies demonstrated that prostaglandin E2 (PGE2) participates in the regulation of glomerular and distal tubular function. A functional role for PGE2 on the proximal tubule has only recently been explored. Thus, we reported that PGE2 antagonizes the phosphaturic effect of PTH in the dog, which suggests that PGE2 may influence the transport functions of the mammalian proximal tubule. The present studies were designed to examine the direct effect of parathyroid hormone (PTH) and PGE2 on the fluxes of fluid (Jv) and phosphate (Jl-b PO4) in the rabbit proximal convoluted and straight tubules (PCT and PST). The activation of adenylate cyclase by the two agents was also examined. Finally, the combined effects of PTH and PGE2 on Jv and Jl-b PO4 were also studied in the PST. In the PCT, PTH (1 μg/ml) inhibited Jv by 31% (P < 0.05) but did not alter Jl-b PO4. PGE1 (10-5 M) failed to act on either Jv or Jl-b PO4. In this segment, PTH stimulated adenylate cyclase but PGE2 did not. In the PST, PTH (1 μg/ml) inhibited Jv and Jl-b PO4 by 34 and 20%, respectively (P < 0.01). PGE2 (10-5 M) also inhibited Jv and Jl-b PO4. by 33 and 12%, respectively (P < 0.02). In contrast, PGF(2α), a related prostanoid, failed to influence these transport parameters. In the PST, PTH activated adenylate cyclase but PGE2 failed to do so. When both PTH (1 μg/ml) and PGE2 (10-7 M) were present simultaneously, Jv and Jl-b PO4 were comparable to that seen during control collections. Yet, when PGE2 was removed, Jv and Jl-b PO4 were inhibited by PTH by 15 and 24%, respectively (P < 0.05). These observations demonstrate that both PTH and PGE2 independently inhibit phosphate and fluid transport in the PST. While the action of PTH appears to be mediated by cyclic adenosine 3',5' monophosphate (cAMP), the action of PGE2 is not. In the PST, PGE2 also antagonizes the effect of PTH on Jv and Jl-b PO4. This antagonistic action of PGE2 might be associated with its inhibitory effect on adenylate cyclase in the PST. These results, therefore, provide evidence for a dual role of PGE2 in the PST. On the one hand, the acid lipid appears to act in the PST as a stimulatory agonist in a manner that resembles PTH. Yet, when both PGE2 and PTH are present together, the prostanoid antagonizes the effects of PTH on both fluid and phosphate transport in the rabbit PST. We conclude that these two functions of PGE2 may participate in the intrarenal regulation of transport in the proximal tubule.
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