Figure 2.

A summary of P2 receptor regulation of sodium transport throughout major segments of the nephron. Panel A (Proximal Tubule): Activation of apical P2Y₁ and P2Y₂ receptors by luminal ATP inhibits the activity of the Na⁺/H⁺ exchanger. P2Y₂ receptor activation can also inhibit Na⁺/K⁺ ATPase in the basolateral membrane. Panel B (Medullary thick ascending limb): Basolateral P2X₄ and apical P2Y₂ receptor stimulation by ATP causes an increase in intracellular nitric oxide, that reduces sodium reabsorption through mechanisms of inhibiting the Na⁺/H⁺ exchanger, N⁺/K⁺/2Cl⁻ co-transporter, and the Na⁺/K⁺ ATPase. Panel C (Distal Tubule): P2 receptors in the distal tubule cause both an inhibition and stimulation of epithelial sodium channel (ENaC) activity. Activation of basolateral and apical P2Y₂ receptors reduces sodium transport through inhibition of ENaC activity. P2X₄ receptor stimulation by ATP causes an increase in sodium reabsorption through mechanisms associated with ENaC channel activity. Panel D (Collecting Duct): P2 receptor activation by ATP causes a reduction or stimulation in sodium reabsorption in a collecting duct cell. Apical and basolateral P2Y₂, and basolateral P2X₄ receptor, at high levels of ATP, activity inhibits ENaC activity, reducing sodium transport. Low levels of ATP may stimulate ENaC activity through mechanisms linked to P2X₄.