Effect of adenosine on the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule.
The regulation of the furosemide-sensitive Na+-ATPase activity and ouabain-sensitive (Na+ + K+)ATPase activities from proximal tubules by adenosine was investigated. When the concentration of adenosine was increased the furosemide-sensitive ATPase activity decreased with maximal inhibition at 10(-8) M (56% of inhibition). However, the (Na+ + K+)ATPase activity was not affected by adenosine. Theophylline, an antagonist of P1 adenosine receptor, completely reversed the effect of adenosine on the furosemide-sensitive ATPase activity in a dose-response manner. The adenosine effect was mimicked by N6-cyclohexyladenosine (CHA), an agonist for A1 adenosine receptor. 5'-N-ethylcarboxamideadenosine (NECA), an agonist for A2 adenosine receptor, did not affect the furosemide-sensitive ATPase activity. When adenosine was used in the presence of 1 microg ml(-1) pertussis toxin, a Gi protein inhibitor, no change in the furosemide-sensitive ATPase activity was observed. The addition of 1 nM cholera toxin increased the Na+-ATPase activity by 60%. Adenosine decreased the cholera toxin stimulated Na+-ATPase in 42%, similar to the effect observed in the absence of cholera toxin. Dibutyryl-cAMP reversed the effect of adenosine in a dose dependent manner while the protein kinase A peptide inhibitor mimicked it. These data are compatible with a modulatory effect of adenosine on the Na+-ATPase activity via A1 subtype receptor.
Caruso-Neves
C
C
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Francisco-Pedro
L G
LG
Souza
L P
LP
Chagas
C
C
Lopes
A G
AG
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007672:Kidney Cortex / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D013806:Theophylline / Q000494:pharmacology
D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D010042:Ouabain; D003994:Bucladesine; D005665:Furosemide; D002772:Cholera Toxin; D013806:Theophylline; D017868:Cyclic AMP-Dependent Protein Kinases; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine