A BRAIN Na+, K+-ATPASE INHIBITOR (ENDOBAIN E) ENHANCES NOREPINEPHRINE RELEASE IN RAT HYPOTHALAMUS

VATTA MS; PEÑA C; FERNADEZ BE; RODRIGUEZ DE LORES ARNAIZ G

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 1999 vol. 90 p. 573 - 579

0306-4522

We have shown that synaptosomal membrane Na+, K+-ATPase activity is stimulated orinhibited by norepinephrine according to the presence or absence of a brain soluble fraction. Gel filtrationof such soluble fraction has allowed the separation of two fractions, peaks I and II, able to stimulate andinhibit Na+, K+-ATPase activity, respectively. Peak II behaves much like ouabain, which has suggestedthe term endobain. From peak II, a subfraction termed II-E (endobain E), which highly inhibits Na+,K+-ATPase, has been separated by anionic exchange chromatography in a Synchropack AX-300 column.We determined the in vitro effect of endobain E obtained from rat cerebral cortex on neuronalnorepinephrine release by incubating rat hypothalamic tissue in the presence of [3H]norepinephrine.Neuronal norepinephrine release was quantified as the factor above basal [3H]norepinephrine released tothe medium at experimental and three post-experimental periods. Endobain E was found to increasenorepinephrine release in a concentration-dependent fashion, reaching 200%, equivalent to the effectachieved with 400 μM ouabain. Ouabain effect persisted along three post-experimental periods whereasthat of endobain E remained only during the first post-experimental period.These results led us to conclude that endobain increases norepinephrine release in hypothalamicneurons at the presynaptic nerve ending level, an effect resembling that of ouabain. It is postulated thatendobain E may enhance catecholamine availability in the synaptic gap, leading to an increase innoradrenergic activity.