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 A1 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 A2 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 A2 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)M cholera 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.
Gomes
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CP
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro,CCS Bloco G, 21949-900, Rio de Janeiro, RJ, Brazil.
Leão-Ferreira
L R
LR
Caruso-Neves
C
C
Lopes
A G
AG
D000241:Adenosine / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D043683:Receptors, Adenosine A2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D027682:Cation Transport Proteins; D043683:Receptors, Adenosine A2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D000241:Adenosine