Rabbit cortical collecting ducts express a novel prostacyclin receptor.
Prostaglandin E2 (PGE2) inhibits vasopressin-stimulated water conductivity (AVP-Lp) 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 (PGI2) has also been shown to inhibit Na+ reabsorption in the CCD. The present studies were designed to examine the effect of the PGI2 agonist, Iloprost (ILP), on AVP-Lp and [Ca2+ in the isolated perfused rabbit CCD and to determine whether ILP activates different receptors than PGE2. ILP and PGE2 each maximally inhibited AVP-Lp equipotently at 10(-7) M. When CCDs were exposed to PGE2 and ILP simultaneously, or if PGE2 was added in the presence of ILP, inhibition of AVP-Lp was additive. Additivity was not observed if the PGI2 agonist, carbaprostacyclin (c-PGI2), was added with ILP, or if the PGE2 agonist, sulprostone, was added with PGE2, or if ILP was added to CCDs preexposed to PGE2. In fura 2-loaded CCD, ILP and PGE2 added separately increased [Ca2+]i. The response to c-PGI2 could be desensitized by prior exposure to ILP. ILP did not cause desensitization to PGE2, but PGE2 could desensitize the CCD to ILP. We conclude that PGI2 inhibits AVP-Lp 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 PGI2 cannot occupy PGE2 receptors and that PGE2 can occupy but cannot activate PGI2 receptors linked to inhibition of AVP-Lp.
Hébert
R L
RL
Department of Physiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Regnier
L
L
Peterson
L N
LN
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004347:Drug Interactions; D004553:Electric Conductivity; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism* / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011817:Rabbits; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000096:biosynthesis* / Q000502:physiology; D013997:Time Factors
D011465:Prostaglandins, Synthetic; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D001127:Arginine Vasopressin; C026678:carboprostacyclin; D011464:Epoprostenol; D016285:Iloprost; D015232:Dinoprostone; D002118:Calcium