Inhibition of renal Na+-ATPase activity by inosine is mediated by A1 receptor-induced inhibition of the cAMP signaling pathway

• Published in: Archives of biochemistry and biophysics Vol. 489; no. 1-2; pp. 76 - 81
• Main Authors: Assaife-Lopes, Natália, Wengert, Mira, de Sá Pinheiro, Ana Acacia, Leão-Ferreira, Luiz Roberto, Caruso-Neves, Celso
• Format: Journal Article
• Language: English
• Published: United States 01.09.2009
• Subjects: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Adenosine A3 Receptor Antagonists; Adenosine Triphosphatases - antagonists & inhibitors; Adenosine Triphosphatases - metabolism; Animals; Cation Transport Proteins - antagonists & inhibitors; Cation Transport Proteins - metabolism; Cyclic AMP - metabolism; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Activators - pharmacology; Enzyme Inhibitors - pharmacology; Inosine - pharmacology; Kidney Tubules, Proximal - enzymology; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A3 - metabolism; Receptors, Adenosine A2 - metabolism; Second Messenger Systems - drug effects; Swine; Xanthines - pharmacology
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2009.07.003

We have previously demonstrated that adenosine is deaminated to inosine in the isolated basolateral membrane (BLM) of kidney proximal tubules. This work investigates the possible effect of inosine on proximal tubule Na(+)-ATPase activity. Inosine reduced Na(+)-ATPase activity by 70%. This effect of inosine was completely attenuated by 10(-8) M DPCPX, an A(1) receptor-selective antagonist, but it was not affected by either 10(-8) M DMPX or 10(-7) M MRS1523, A(2) and A(3) receptor-selective antagonists, respectively. The inhibitory effect of inosine was blocked by: (1) 10(-6) M GDPbetaS, a trimeric G protein inhibitor; (2) 1microg/ml pertussis toxin, a Gi protein inhibitor; (3) 10(-6) M forskolin, an adenylyl cyclase activator; (4) 10(-9) M cholera toxin, a Gs protein activator; (5) 10(-6)M cAMP. Our results demonstrate that the inhibitory effect of inosine on the sodium pump is mediated by the A(1) receptor/Gi/cAMP pathway.