EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium

We examined the effect of prostaglandin E-2 (PGE(2)) on antidiuretic hormone (ADH)-dependent Na+ transport and cAMP production in isolated frog skin epithelium. ADH caused an increase in transepithelial Na+ transport and a decrease in cellular potential, indicating an increase in apical Na+ permeability. Subsequent addition of PGE(2) decreased Na+ transport and repolarised the cells. The PGE(2) receptor EP1/3-selective analogue sulprostone and the PGE(2) receptor EP2/3-selective analogue misoprostol were able to mimic the effect of PGE(2). ADH increased cellular cAMP levels, whereas PGE(2), sulprostone and misoprostol were able to reduce the ADH-dependent cAMP production. Measurements of intracellular Ca2+ concentration ([Ca2+](i)) revealed that it was unaffected by both PGE(2) and sulprostone. The inhibitory effect of PGE(2) on ADH-dependent Na+ transport was also observed in Ca2+-depleted epithelia. We conclude that ADH stimulates transepithelial Na+ transport by increasing cellular cAMP levels, whereas PGE(2) inhibits ADH-dependent Naf transport by activating EP3-type receptors, which decrease cellular cAMP levels. We have found no evidence that [Ca2+](i) is involved in the regulation of ADH-dependent Na+ transport by PGE(2).