EVIDENCE THAT SEPARATE PGE(2) RECEPTORS MODULATE WATER AND SODIUM-TRANSPORT IN RABBIT CORTICAL COLLECTING DUCT

Prostaglandin E2 (PGE2) modulates both water and sodium transport in t he rabbit cortical collecting duct (CCD). To determine whether these e ffects are mediated by separate PGE2 receptors, we compared the effect s of PGE2 and its analogue sulprostone in the isolated perfused rabbit CCD. PGE2 increased basal water permeability (hydraulic conductivity) , whereas sulprostone did not. PGE2 and sulprostone were equipotent in hibitors of water absorption when it was prestimulated by vasopressin. Pertussis toxin completely reversed the inhibitory effect of sulprost one but only partially reversed the inhibitory effect of PGE2. In cont rast, a protein kinase C (PKC) inhibitor, staurosporine, partially rev ersed the inhibitory effect of PGE2 but had no effect on sulprostone. PGE2 also raised intracellular calcium ([Ca2+]i). This effect is coupl ed to its capacity to inhibit Na+ absorption. Sulprostone was 10-fold less potent than PGE2 both in raising [Ca2+]i or inhibiting sodium tra nsport. The results suggest sulprostone selectively interacts with a P GE2 receptor coupled to pertussis toxin-sensitive inhibition of water permeability. Sulprostone less potently activates a PGE2 receptor coup led to (Ca2+]i, PKC activation, and sodium transport and completely fa ils to interact with the PGE2 receptor that stimulates water permeabil ity in the collecting duct. These results suggest distinct PGE2 recept ors modulate sodium and water transport in the CCD.