Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9890132 | The International Journal of Biochemistry & Cell Biology | 2005 | 11 Pages |
Abstract
The aim of this work was to determine the molecular mechanism involved in the stimulation of the pig kidney proximal tubule Na+-ATPase by adenosine (Ado). To study the role of A2 Ado receptors, we added in all experiments 10â6 M DPCPX, an A1 receptor-selective antagonist, since we have previously shown that Ado inhibits the enzyme activity through this receptor. Ado increased the Na+-ATPase activity with maximal effect observed at 10â6 M. The presence of both A2A and A2B receptors were demonstrated by immunoblotting using specific polyclonal antibodies. The stimulatory effect of Ado was completely abolished by 5 à 10â9 M DMPX, an antagonist of A2 receptor, and 10â7 M SCH 58261, an A2A receptor-selective antagonist. DMPA (10â7 M), a specific agonist of A2A receptor mimicked the stimulatory effect of Ado. Involvement of a Gs protein/adenylate cyclase/PKA pathway was evidenced by: (a) the reversion of Ado-induced effect by GDPβS; (b) stimulation of the Na+-ATPase activity in a similar and non-additive manner to Ado by 10â8 M cholera toxin, 10â7 M GTPγS, 10â6 M forskolin, 10â7 M cAMP or 1.25U catalytic subunit of PKA; (c) the reversion of the stimulatory effect of Ado by 10â8 M PKA inhibitor peptide; (d) Ado-produced two-fold increase of the PKA activity, which was completely reversed by 10â6 M DMPX. These are the first evidences showing the modulation of a renal primary active sodium transporter by Ado through A2A receptor.
Keywords
DMPXSCH 58261GDPβSGTPγSNECATRISCTXforskolinDPCPXpKaPMSFFskDPMAADOtris(trishydroxymethyl)-aminomethaneHEPES3,7-dimethyl-1-propargylxanthine5′-N-ethylcarboxamidoadenosine8-Cyclopentyl-1,3-dipropylxanthinecAMPguanosine 5′-O-(2-thiodiphosphate)guanosine 5′-O-(3-thiotriphosphate)Na+-ATPaseAdenosineadenosine 3′,5′-cyclic monophosphateadenosine triphosphate (sodium salt)ATPEDTAEthylenediaminetetraacetic acidcholera toxinphenylmethylsulfonyl fluorideproximal tubuleAdenosine receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
M. Wengert, C. Jr., J. Kaufman, L.R. Leão-Ferreira, R. Paes-de-Carvalho, A.G. Lopes, C. Caruso-Neves,