Aspects of renal water transport in P2Y2 knockout mice (P2Y2−/−) under basal conditions (basal), in response to acute vasopressin V2 receptor inhibition (V2-I), acute water loading (WL) or WL plus pretreatment with indomethacin (WL+Indo). A, C: compared with basal measurements, V2-I increased urinary flow rate and electrolyte free-water clearance (Cle-H2O) to a greater extent in P2Y2−/− vs. wild-type (WT) mice (determined over a 2-h period after intraperitoneal application of the receptor inhibitor). These findings indicated greater water reabsorption but also the basal delivery of greater amounts of more hypotonic fluid to the distal nephron in P2Y2−/−. This could explain the facilitated Cle-H2O in response to water loading in P2Y2−/−, i.e., less suppression of vasopressin and/or cAMP is sufficient to increase Cle-H2O to the same extent as in WT (not shown). B: Increases in urinary PGE2 after oral water loading (3% of body weight) were much greater in P2Y2−/−; treatment with indomethacin reduced urinary PGE2 excretion in water-loaded P2Y2−/− to levels of WT mice without indomethacin treatment; urinary flow rate and electrolyte-free water clearance (Cle-H2O) were unaffected in P2Y2−/− mice compared with untreated. *P < 0.05 vs. WT; data for WL+Indo are unpublished; the other data are from Ref. 59.