Fig. 9. A model for the involvement of Rho in prostaglandin E₂ (PGE₂)-antagonized vasopressin-mediated water reabsorption. Vasopressin (AVP) facilitates water reabsorption in renal collecting duct principal cells by binding to vasopressin V2 receptors (V2R). The agonist-occupied V2R activates adenylyl cyclase (AC) via the G protein G_s. The resulting increase in cAMP leads to activation of protein kinase A (PKA), phosphorylating AQP2 and Rho. Rho phosphorylation decreases its activity, resulting in the depolymerisation of F-actin and facilitating the insertion of AQP2 predominantly into the apical plasma membrane. Stimulation of EP₃ receptors by PGE₂, achieved by incubation of IMCD cells with a combination of the PGE₂ analogue sulprostone, an EP₁/EP₃ receptor agonist and the EP₁ receptor antagonist SC19220, induces the activation of Rho, most probably via the G proteins G_12/13. Rho activation is independent of increases in cAMP and cytosolic Ca²⁺. It promotes the formation F-actin which hinders AQP2-bearing vesicles reaching the plasma membrane by acting as a physical barrier. EP₃ receptor-mediated activation of the G protein G_i, inhibiting adenylyl cyclase, is unlikely to contribute to the diuretic effect of PGE₂. In the presence of AVP, the EP₃ receptor-induced Rho activation and inhibition of AQP2 translocation are attenuated by EP₁ receptor stimulation; the underlying signaling pathway is not known.

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