ATP can be detected in urine at concentrations sufficient to activate P2 receptors (P2Rs) expressed in the luminal membrane of renal tubular cells (Unwin et al. 2003). The activation of certain apical P2Rs by extracellular ATP has been shown to inhibit Na⁺ transport in the collecting duct (CD) in vitro and in vivo. Previously, using the Xenopus oocyte expression system, we have demonstrated a regulatory interdependence between certain P2Rs and the epithelial Na⁺ channel (ENaC) (Wildman et al. 2005). We have shown that plasma membrane expression of P2R assemblies incorporating P2X₂, P2X₅ and P2X₆ subunits are directly increased by ENaC expression and that ENaC activity is decreased by the stimulation of P2R assemblies incorporating P2X₂, P2X₄ and P2X₆ subunits. We have proposed that some P2Rs may provide localised and fine regulation of ENaC activity in the CD in vivo. Kidneys from terminally anaesthetised adult Sprague Dawley rats (maintained on low (0.01%), normal (0.5%) or high (4%) sodium diets, for 10 days) were perfusion-fixed with paraformaldehyde (4%) and sliced (8 µm). We used co-immunofluorescence (using an AQP2 antibody as a marker of the CD) to investigate apical P2R expression patterns along the CD in response to changes in dietary sodium intake (that also change ENaC expression). In rats maintained on a normal Na⁺ diet (n=3), immunostaining for P2X₄ and P2X₆ ion channel receptor subunits and P2Y₄, P2Y₆, P2Y₁₁ and P2Y₁₂ metabotropic receptors was evident in the apical membrane throughout the CD. Weak staining was seen for apical P2X₂, P2X₅ and P2X₇ receptors. In rats on a low Na⁺ diet (n=3), expression of P2X₁ also became apparent, expression of P2X₂ was increased and immunostaining for P2X₅ disappeared. With the exception of P2Y₄, all previously detected P2Y receptors showed restricted co-localisation and weak apical staining. A high Na⁺ diet also resulted in increased apical expression of P2X₁, but in contrast to normal and low Na⁺ diets expression of apical P2X₇ receptors was increased and immunostaining for P2X₂ disappeared. We also saw weak staining for those P2Y receptors previously detected in abundance, with exception of P2Y₆ and P2Y₁₂, which remained unchanged. In summary, apical P2R expression patterns change in the rat CD in response to changes in dietary sodium intake. Our results support a link between P2R expression and function and ENaC regulation (i.e. assemblies of P2X₂, P2X₄ and P2X₆ subunits, having the ability to inhibit ENaC activity, shown here to mirror ENaC expression in vivo), which, itself, is regulated by levels of dietary Na⁺.