Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 489, Issue 1-2, Pages 76-81Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.07.003
Keywords
Inosine; Na+-ATPase; Proximal tubule; cAMP; PKA
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq
- Programa de Apoio a Nucleos de Excelencia - PRONEX/CNPq
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro - FAPERJ
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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 GDP beta S, a trimeric G protein inhibitor; (2) 1 mu g/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. (C) 2009 Elsevier Inc. All rights reserved.
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