Prostaglandin E2 and parathyroid hormone: Comparisons of their actions on the rabbit proximal tubule

Prostaglandin E 2 and parathyroid hormone: Comparisons of their actions on the rabbit proximal tubule. Recent studies demonstrated that prostaglandin E 2 (PGE 2 ) participates in the regulation of glomerular and distal tubular function. A functional role for PGE 2 on the proximal tubule has only recently been explored. Thus, we reported that PGE 2 antagonizes the phosphaturic effect of PTH in the dog, which suggests that PGE 2 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 PGE 2 on the fluxes of fluid (Jv) and phosphate (Jl-b PO 4 ) 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 PGE 2 on Jv and Jl-b PO 4 were also studied in the PST. In the PCT, PTH (1 µg/ml) inhibited Jv by 31% (P 4 . PGE 2 (10 -5 M) failed to act on either Jv or Jl-b PO 4 . In this segment, PTH stimulated adenylate cyclase but PGE 2 did not. In the PST, PTH (1 µg/ml) inhibited Jv and Jl-b PO 4 by 34 and 20%, respectively (P 2 (10 -5 M) also inhibited Jv and Jl-b PO 4 , by 33 and 12%, respectively (P 2α , a related prostanoid, failed to influence these transport parameters. In the PST, PTH activated adenylate cyclase but PGE 2 failed to do so. When both PTH (1 µg/ml) and PGE 2 (10 -7 M) were present simultaneously, Jv and Jl-b PO 4 were comparable to that seen during control collections. Yet, when PGE 2 was removed, Jv and Jl-b PO 4 were inhibited by PTH by 15 and 24%, respectively (P 2 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 PGE 2 is not. In the PST, PGE 2 also antagonizes the effect of PTH on Jv and Jl-b PO 4 . This antagonistic action of PGE 2 might be associated with its inhibitory effect on adenylate cyclase in the PST. These results, therefore, provide evidence for a dual role of PGE 2 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 PGE 2 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 PGE 2 may participate in the intrarenal regulation of transport in the proximal tubule. Prostaglandines E 2 et hormone parathyroidienne: Comparaisons de leurs effets sur le tubule proximal de lapin. Des etudes recentes ont demontre que la prostaglandine E 2 (PGE 2 ) participe a la regulation des fonctions glomerulaire et tubulaire distale. Un role fonctionnel de la PGE 2 sur le tubule proximal a ete explore seulement recemment. Ainsi, nous avons rapporte que la PGE 2 antagonise l'effet phosphaturique de la PTH chez le chien. Ce resultat suggere que la PGE 2 pourrait influencer les fonctions de transport dans le tubule proximal de mammifere. Ces etudes ont ete entreprises pour examiner l'effet direct de l'hormone parathyroidienne (PTH) et de la PGE 2 sur les flux de liquide (Jv) et de phosphate (Jl-b PO 4 ) dans des tubules contournes et droits proximaux (PCT et PST) de lapin. L'activation de l'adenylate cyclase par les deux agents a egalement ete examinee. Enfin, les effets combines de PTH et PGE 2 sur Jv et Jl-b PO 4 ont egalement ete etudies dans le PST. Dans le PCT, la PTH (1 µg/ml) a inhibe Jv de 31% (P 4 . La PGE 2 (10 -5 M) n'a agi ni sur Jv, ni sur Jl-b PO 4 . Dans ce segment, la PTH a stimule l'adenylate cyclase, ce que n'a pas fait la PGE 2 . Dans le PST, la PTH (1 µg/ml) a inhibe Jv et Jl-b PO 4 de 34 et 20%, respectivement (P 2 (10 -5 M) a aussi inhibe Jv et Jb-b PO 4 de 33 et 12%, respectivement (P 2α , un prostanoide apparente, n'a pas influence ces parametres de transport. Dans le PST, la PTH a active l'adenylate cyclase, ce que la PGE 2 n'a pu faire. Lorsque les deux agents, la PTH (1 µg/ml) et la PGE 2 (10 -7 M) etaient presents simultanement, Jv et Jl-b PO 4 etaient comparables aux valeurs observees pendant les recueils controles. Cependant, lorsque la PGE 2 etait enlevee, Jv et Jl-b PO 4 etaient inhibes par la PTH de 15 et de 24%, respectivement, P 2 inhibent toutes les deux independamment le transport de phosphate et de liquide dans le PST. Alors que l'action de la PTH semble mediee par l'adenosine 3′, 5′ monophosphate cyclique (cAMP), l'action de la PGE 2 ne l'est pas. Dans le PST, la PGE 2 antagonise egalement l'effet de la PTH sur Jv et Jl-b PO 4 . Cet effet antagoniste de la PGE 2 pourrait etre lie a son effet inhibiteur de l'adenylate cyclase dans le PST. Ainsi, ces resultats apportent la preuve d'un effet double de la PGE 2 dans le PST. D'un cote, ce lipide acide semble agir dans le PST comme un agoniste stimulateur d'une facon ressemblant a celle de la PTH. Cependant, quand les deux agents, la PGE 2 et la PTH sont presents ensemble, le prostanoide antagonise les effets de la PTH sur le transport de liquide et de phosphate dans le PST de lapin. Nous concluons que ces deux roles de la PGE 2 pourraient contribuer a la regulation intrarenale du transport dans le tubule proximal.