Adenosine reverses the stimulatory effect of angiotensin II on the renal Na(+)-ATPase activity through the A(2) receptor.

摘要

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 Pixmg(-1)xmin(-1)nmol Pixmg(-1)xmin(-1) (p<0.05). Incubation of Ang II-stimulated enzyme with 10(-6)M Ado, in the presence of the A(1) receptor antagonist DPCPX (10(-6)M), 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 GDPbetaS and mimicked by 10(-9)Mcholera toxin and 10(-8)M GTPgammaS; 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.