Arginine-Vasopressin Modulates Intracellular pH via V1 and V2 Receptors in Renal Collecting Duct Cells

Arginine-vasopressin (AVP) has been proposed to be involved in the modulation of acid-base transporters; however, the nature of the mechanisms underlying AVP direct action on intracellular pH (pH i ) in the cortical collecting duct (CCD) is not yet clearly defined. The aim of the present study was to elucidate which are the proteins implicated in AVP modulation of pH i , as well as the receptors involved in these responses using a CCD cell line (RCCD 1 ); pH i was monitored with the fluorescent dye BCECF in basal conditions and after stimulation with basolateral 10 -8 M AVP. Specific V1- or V2-receptor antagonists were also used. RT-PCR studies demonstrated that RCCD 1 cells express V1a and V2 receptors. Functional studies showed that while V2-receptor activation induced a biphasic response (alkalinization-acidification), V1-receptor activation resulted in an intracellular acidification. The V2-mediated alkalinization phase involves the activation of basolateral NHE-1 isoform of the Na + /H + exchanger while in the acidification phase CFTR is probably implicated. On the other hand, V1-mediated acidification was due to activation of a Cl - /HCO 3 - exchanger. We conclude that in RCCD 1 cells AVP selectively activates, via a complex of V1 and V2 receptor-mediated actions, different ion transporters linked to pH i regulation which might have physiological implications.