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

 We examined the effect of prostaglandin E₂ (PGE₂) 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 PGE₂ decreased Na⁺ transport and repolarised the cells. The PGE₂ receptor EP_1/3-selective analogue sulprostone and the PGE₂ receptor EP_2/3-selective analogue misoprostol were able to mimic the effect of PGE₂. ADH increased cellular cAMP levels, whereas PGE₂, 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 PGE₂ and sulprostone. The inhibitory effect of PGE₂ 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 PGE₂ inhibits ADH-dependent Na⁺ 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 PGE₂. Received: 27 May 1998 / Received after revision: 18 August 1998 / Accepted: 1 September 1998