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We have previously reported that Na+,K+-ATPase of nerve ending membranes is stimulated by catecholamines only in the presence of a brain soluble fraction. The filtration of this soluble fraction through Sephadex G-50 permitted the separation of two extracts of maximal UV absorbance (peaks I and II) which showed different effects on ATPases. Peak I stimulated both Na+, K+-ATPase and Mg2+-ATPase activities and peak II inhibited Na+, K+-ATPase activity. We have now studied the activity of ATPases in the presence of the whole eluate obtained from the Sephadex G-50 column. It was observed that maximal effects on ATPases were obtained with peaks I and II. Peak I and peak II fractions were unable to modify the activity of acetylcholinesterase or 5'-nucleotidase present in the synaptosomal membranes. The stimulatory effect of peak I on ATPases was concentration dependent (up to 1:100), it was stable at different pHs and it was reverted by catecholamines. The inhibitory effect of peak II on Na+,K+-ATPase was concentration dependent (up to 1:50,000), it was stable only at acid pH, and it was partially reverted by catecholamines. These findings indicate that the factors responsible for the effects of peaks I and II have different properties and that their actions on ATPases show enzyme specificity.

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Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required to maintain cellular Na+/K+ gradients through the participation of the sodium pump (Na+,K+-ATPase), whose activity is selectively and potently inhibited by the alkaloid ouabain. Na+/K+ gradients are involved in nerve impulse propagation, in neurotransmitter release and cation homeostasis in the nervous system. Likewise, enzyme activity modulation is crucial for maintaining normal blood pressure and cardiovascular contractility as well as renal sodium excretion. The present article reviews the progress in disclosing putative ouabain-like substances, examines their denomination according to different research teams, tissue or biological fluid sources, extraction and purification, assays, biological properties and chemical and biophysical features. When data is available, comparison with ouabain itself is mentioned. Likewise, their potential action in normal physiology as well as in experimental and human pathology is summarized.