Adenosine reverses the stimulatory effect of angiotensin II on the renal Na+-ATPase activity through the A2 receptor

In the present paper, we report the modulation of the Angiotensin II (Ang II)-stimulated Na+-ATPase activity of the proximal tubule basolateral membrane by adenosine (Ado). Preincubation of isolated basolateral membrane with 10(-8)M Ang II increases the Na+-ATPase activity from 7.5 +/- 0.3 (control) to 14.6 +/- 0.9 nmol Pi x mg(-1) x min(-1) nmol Pi x mg(-1) x min(-1) (p < 0.05). Incubation of Ang II-stimulated enzyme with 10(-6)M Ado, in the presence of the A, receptor antagonist DPCPX (10-6M), completely reverses the Ang II-induced effect bringing the Na+-ATPase activity to the basal level. The following evidences demonstrate involvement of the A(2) receptor/Gs protein/adenylyl cyclase/PKA signaling pathway in the inhibitory effect induced by Ado on the Ang II-stimulated Na+-ATPase activity in the presence of the DPCPX: 1) the inhibitory effect of Ado is abolished by the A(2) receptor selective antagonist DMPX (10(-8)M); 2) the effect induced by Ado is blocked by 10(-8)M GDP beta S and mimicked by 10(-9)M cholera toxin and 10(-8)M GTP gamma S; 3) the stimulatory effect of Ang II is reduced by 10(-6)M forskolin. an activator of adenylyl cyclase, or 10(-6)M cAMP; 4) Ado stimulates PKA activity; 5) the inhibitory effect induced by this nucleoside is reversed by the PKA inhibitor peptide. (c) 2005 Elsevier B.V. All rights reserved.