Journal of Bioequivalence & Bioavailability

Abstract

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

Sinerik Ayrapetyan, Armenuhi Heqimyan and Anna Nikoghosyan

Tissue hydration, dose-dependent 3H-ouabain binding, 45Ca2+ exchange in rat�s brain cortex, subcortex and cerebellum were studied in three age groups. Age-dependent tissue dehydration in all three zones of brain was due to inhibition of Na+/K+ pump. The age-dependence of cell hydration in cortex was more expressed. The curve of dose-dependent ouabain binding consists of three components corresponding to Na+/K+ pump isoforms (α1, α2, α3). Age-dependency of these isoforms was more expressed in cortex than in subcortex and cerebellum. High affinity receptors were depressed in old rats� brain tissues. Initial 45Ca2+ uptake in three brain zones of old rats was depressed as compared to that of young animals. Ouabain at 10-9 M has activation effect on 45Ca2+ uptake, which was also age dependent. Initial 45Ca2+ efflux in cortex and subcortex tissue in old rats was significantly depressed as compared to young ones while in cerebellum the opposite age-dependence was observed. The curves of dose-dependent ouabain effect on 45Ca2+ efflux and cell hydration consist of 6 components. However, close correlation between kinetics of 45Ca2+ efflux and cell hydration was not observed. It is suggested that brain tissue dehydration in aged animals is a consequence of Na+/K+ pump dysfunction induced intracellular calcium elevation. It is suggested that α3 receptors are functionally connected with intracellular Ca2+ buffering systems through intracellular signaling systems and their dysfunction in aged brain is a consequence of [Ca2+]i increase. Obtained data allow us to conclude that endogen nanomolar ouabain-like species circulating in mammals� blood removing Ca2+ from cells could have a beneficial effect on brain of old animals.