RABBIT CORTICAL COLLECTING DUCTS EXPRESS A NOVEL PROSTACYCLIN RECEPTOR

Prostaglandin E(2) (PGE(2)) inhibits vasopressin-stimulated water conductivity (AVP-L(p)) and inhibits Na+ reabsorption in the rabbit cortical collecting duct (CCD). Inhibition of Na+ reabsorption is mediated by increased intracellular calcium ion concentration ([Ca2+](i)). Prostacyclin (PGI(2)) has also been shown to inhibit Na+ reabsorption in the CCD. The present studies were designed to examine the effect of the PGI(2) agonist, Iloprost (ILP), on AVP-L(p) and [Ca2+](i) in the isolated perfused rabbit CCD and to determine whether ILP activates different receptors than PGE(2). ILP and PGE(2) each maximally inhibited AVP-L(p) equipotently at 10(-7) M. When CCDs were exposed to PGE(2) and ILP simultaneously, or if PGE(2) was added in the presence of ILP, inhibition of AVP-L(p) was additive. Additivity was not observed if the PGI(2) agonist, carbaprostacyclin (c-PGI(2)), was added with ILP, or if the PGE(2) agonist, sulprostone, was added with PGE(2), or if ILP was added to CCDs preexposed to PGE(2). In fura 2-loaded CCD, ILP and PGE(2) added separately increased [Ca2+](i). The response to c-PGI(2) could be desensitized by prior exposure to ILP. ILP did not cause desensitization to PGE(2), but PGE(2) could desensitize the CCD to ILP. We conclude that PGI(2) inhibits AVP-L(p) by activation of a novel IP3 prostacyclin receptor and increases [Ca2+](i) by activation of an IP1 prostacyclin receptor in the rabbit CCD. Functional evidence is presented that PGI(2) cannot occupy PGE(2) receptors and that PGE(2) can occupy but cannot activate PGI(2) receptors linked to inhibition of AVP-L(p).