An endogenous Na+, K+-ATPase inhibitor enhances phosphoinositide hydrolysis in neonatal but not in adult rat brain cortex.
The effect of an endogenous Na+, K+-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in rat brain cortical prisms and compared with that of ouabain. As already shown for ouabain, a transient effect was obtained with endobain E; maximal accumulation of inositol phosphates induced by endobain E was 604 +/- 138% and 186 +/- 48% of basal values in neonatal and adult rats, respectively. The concentration-response plot for the interaction between endobain E and phosphoinositide turnover differed from that of ouabain, thus suggesting the involvement of distinct mechanisms. In the presence of endobain E plus ouabain at saturating concentrations, no additive effect was recorded, suggesting that both substances share at least a common step in their activation mechanism of inositol phosphates metabolism or that they enhance phosphatidylinositol 4,5-biphosphate breakdown from the same membrane precursor pool, until its exhaustion. Experiments with benzamil, a potent blocker of Na+/Ca2+ exchanger, showed that it partially and dose-dependently inhibited endobain E effect. These results indicate that the endogenous Na+, K+-ATPase inhibitor endobain E, like ouabain, is able to stimulate phosphoinositide turnover transiently during postnatal brain development.
Calviño
M A
MA
Instituto de Biología Celular y Neurociencias Prof. E. De Robertis, PROBICENE-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Peña
C
C
Rodríguez de Lores Arnaiz
G
G
D000375:Aging / Q000502:physiology*; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000031:analogs & derivatives* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D010716:Phosphatidylinositols; C119205:endobain E; C013407:benzamil; D010042:Ouabain; D000584:Amiloride; D002217:Carbachol; D000254:Sodium-Potassium-Exchanging ATPase