Attenuation of Lithium-induced Natriuresis and Kaliuresis in P2Y2 Receptor Knockout Mice.

Attenuation of Lithium-induced Natriuresis and Kaliuresis in P2Y2 Receptor Knockout Mice. Am J Physiol Renal Physiol. 2013 Jun 5; Authors: Zhang Y, Li L, Kohan DE, Ecelbarger CM, Kishore BK Abstract Whole-body knockout (KO) of the P2Y2 receptor (R) results in enhanced vasopressin V2-receptor activity and increased renal sodium conservation. We hypothesized that P2Y2-R KO mice would be less sensitive to Li-induced natriuresis and kaliuresis due to attenuated down-regulation of one or more of the major renal sodium or potassium transporter/channel proteins. KO and wild-type (WT) mice were fed control (C) or Li-added diet (40 mmol/kg food) for 14 days. Li-induced natriuresis and kaliuresis were significantly (>50%) attenuated in the KO mice. The subunits of the epithelial sodium channel (ENaC) were variably affected by Li and genotype, but overall, medullary levels were decreased substantially by Li (15-60%) in both genotypes. In contrast, cortical, β- and γ-ENaC were increased by Li (~50%), but only in the WT. Moreover, an assessment of ENaC activity by benzamil sensitivity suggested Li increased ENaC activity in WT, but not KO mice. In contrast, medullary levels of the Na-K-2Cl cotransporter (NKCC2) and cortical levels of the renal outer medullary potassium channel (ROMK) were not down-regulated by Li, and significantly (15-76%) higher in the KO mice under both dietary conditions. In addition, under control conditions, the tissue osmolalit...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research