FIGURE 9.

A proposed model for cell volume-dependent ATP release and water transport inhibition by P2Y₂ receptor activation in inner medullary collecting duct (IMCD) cells. Arginine vasopressin (AVP) activates vasopressin V₂ receptor (V₂R) to stimulate aquaporin-2-mediated water entry which increases cell volume. The latter increases basolateral and apical release of ATP (and potentially UTP?) by unknown mechanisms. P2Y₂ receptor activation inhibits water reabsorption via multiple signaling pathways (see text for details) and stimulates volume regulatory potassium channels as shown in other cell types. In response to water loading, the ATP/UTP/P2Y₂ receptor system maintains cell volume, which tends to increase by the relative hypotonic extracellular fluid, and accelerates the excretion of free water before circulating AVP levels drop. AC, adenylyl cyclase; AQP2, -3, -4, aquaporin-2, -3, -4; COX1, cyclooxygenase 1; CREB, cAMP responsive element binding protein; Cx37, connexin 37; DAG, diacylglycerol; EP₃, PGE₂ E₃ receptor; ET-1, endothelin-1; ET_B, endothelin B receptor; G_i, inhibitory G protein; Gq, G_s, stimulatory G protein; IP₃, inositol trisphosphate; P₂₅₆, P₂₆₁, phosphorylation of AQP2; Panx1, pannexin 1; PGE₂, prostaglandin E₂; PLC, phospholipase C; PKA, protein kinase A; PKC, protein kinase C; Ub, ubiquitin; UT-A1, urea transporter A1. [Modified from Vallon and Rieg (527).]