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Physiological regulation of ENaC activity in the distal nephron by local bradykinin signaling
Author(s) -
Pochynyuk Oleh
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.606.12
Subject(s) - epithelial sodium channel , bradykinin , endocrinology , medicine , reabsorption , aldosterone , chemistry , renal sodium reabsorption , receptor , stimulation , nephron , kidney , sodium , biology , organic chemistry
ENaC activity in the aldosterone‐sensitive distal nephron sets sodium plasma levels to control blood pressure in response to negative feedback regulation by the renin‐angiotensin‐aldosterone system. In complement to this, paracrine factors intrinsic to the collecting duct, including bradykinin (BK), may also have an important role in controlling ENaC‐mediated sodium reabsorption. Patch clamp electrophysiology on freshly isolated murine collecting ducts (CD) was used to test whether ENaC is a proximal target for bradykinin signaling. Bradykinin acutely and reversibly decreases ENaC open probability via B2 receptors: Inhibition of B2 receptors with HOE‐140 prevents BK‐mediated decreases in ENaC P o . Disruption of this paracrine signaling in B2 −/− mice abolishes BK actions on ENaC and results in elevated resting ENaC P o . We propose that sodium retention due to increased basal ENaC activity contributes, in part, to the salt‐sensitive hypertension in B2 −/− mice. B2 receptors couple to both G q/11 ‐PLC, and G αi ‐mediating decreases in adenylyl cyclase activity. Inhibition of PLC with U73122 but not saturation of intracellular [cAMP] with 8‐cpt‐cAMP disrupts regulation of ENaC by BK. Rapid decreases in apical PI(4,5)P 2 levels in response to BK stimulation parallel decreases in ENaC activity. Inhibition of Ca 2+ release from the ER does not prevent decreases in ENaC activity in response to bradykinin. This is consistent with decreases in PI(4,5)P 2 levels but not subsequent increases in intracellular Ca 2+ account for BK‐mediated decreases in ENaC activity in response to stimulation of B2‐G q/11 ‐PLC.