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

Natália Assaife-Lopes; Mira Wengert; Ana Acacia de Sá Pinheiro; Luiz Roberto Leão-Ferreira; Celso Caruso-Neves

doi:10.1016/j.abb.2009.07.003

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

Arch Biochem Biophys. 2009 Sep;489(1-2):76-81. doi: 10.1016/j.abb.2009.07.003. Epub 2009 Jul 12.

Authors

Natália Assaife-Lopes¹, Mira Wengert, Ana Acacia de Sá Pinheiro, Luiz Roberto Leão-Ferreira, Celso Caruso-Neves

Affiliation

¹ Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS Bloco G, 21949 Rio de Janeiro, RJ, Brazil.

PMID: 19709567
DOI: 10.1016/j.abb.2009.07.003

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Antagonists
Cation Transport Proteins
Enzyme Activators
Enzyme Inhibitors
Receptor, Adenosine A1
Receptor, Adenosine A3
Receptors, Adenosine A2
Xanthines
Inosine
1,3-dipropyl-8-cyclopentylxanthine
Cyclic AMP
Adenosine Triphosphatases
sodium-translocating ATPase