Release of ATP by TRPV4 activation is dependent upon the expression of AQP2 in renal cells.

ALEJANDRO PIZZONI; BAZZI ZAHER; DI GIUSTO, GISELA; CORA ALVAREZ; RIVAROLA VALERIA; CAPURRO CLAUDIA; PABLO SCHARZBAUM; PAULA FORD

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2021 vol. 236 p. 2559 - 2571

0021-9541

The involvement of purinergic signalling in kidney physiology and pathophysiology is gaining recognition. In several tissues, ATP release is dependent upon activation of the transient receptor potential cation channel (TRPV4). Because we have recently found that TRPV4 physical and functional interacts with the water channel aquaporin‐2 (AQP2) in cortical collecting ducts cells (CCD), this work aimed to examine the possibility that TRPV4/AQP2 interaction influences ATP release in these cells. We used two rat CCD cell lines expressing AQP2 (AQP2-RCCD1) or not (WT-RCCD1). Extracellular ATP (ATPe) was measured using firefly luciferase and intracellular calcium was estimated with Fura-2. We found that AQP2 is critical for the release of ATP induced by TRPV4 activation. TRPV4-stimulated ATP release occurs by an exocytic and a conductive route. ATPe, in turn, acts in an autocrine and/or paracrine manner stimulating purinergic receptors leading to ATPe-induced ATP release. We also found that ATPe modulates RCCD1 cell migration.