Sympathetic Stimulation In The Kidney: A Possible Antidiuretic Effect Of BAR3?

Abstract

Beta-adrenergic receptors BAR1 and BAR2 regulate important renal functions. However, the presence, localization and possible physiological role of BAR3 in the kidney is still debated. We immunolocalized BAR3 in wt mouse with markers of different nephron segments. Confocal analysis indicated that BAR3 is expressed at the basolateral membrane of the epithelial cells of the thin ascending limb (tAL), thick ascending limb (TAL), distal convolute tubule (DCT) and the cortical and outer medullary collecting duct (CD). The presence of BAR3 in the vasopressin-sensitive nephron segments prompted us to investigate the possible effect of BAR3 stimulation on the plasma membrane expression of the water channel AQP2. We incubated mouse kidney slices either with isoproterenol or with the BAR3 selective agonist BRL37344, in the presence or in the absence of the PKA inhibitor H89 or BAR3 antagonists. To uncover the possible physiological role of BAR3 stimulation in antidiuresis, we injected BRL37344 in mice lacking vasopressin V2 receptor (V2R). Interestingly, in kidney slices, isoproterenol or BRL37344 elicited a vasopressin-like effect on AQP2 trafficking that was counteracted by BAR3 antagonists or H89. Moreover, in V2R-defective mice, BRL37344 promoted a potent antidiuretic effect. Taken together, these findings are of great physiological importance as they uncover the antidiuretic effect of BAR3 stimulation in the kidney and suggest that BAR3 agonists might be useful to bypass V2R inactivating mutations.