Ethanolamine and related amino alcohols increase basal and evoked release of [3H]-D-aspartic acid from synaptosomes by enhancing the filling of synaptic vesicles.

This research examines the effects of ethanolamine and other amino alcohols on the dynamics of acridine orange (AO), oxonol V, and [3H]-D-aspartic acid in synaptic preparations isolated from mammalian brain. Ethanolamine concentration-dependently enhanced AO release from synaptosomes. Similar effects were observed with methylethanolamine and dimethylethanolamine, but not choline. The enhancement of AO efflux by ethanolamine was independent of extrasynaptosomal calcium (in contrast to KCl-induced AO efflux), was unaffected by tetrodotoxin and did not involve depolarization of the synaptosomal plasma membrane. KCl was unable to release AO from synaptosomes following exposure to ethanolamine, however ethanolamine and other amino alcohols were found to enhance both basal and KCl-evoked release of [3H]-D-aspartic acid from synaptosomes. Using isolated synaptic vesicles we demonstrate that amino alcohols are able to 1) abolish the ATP-dependent intravesicular proton concentration (i.e. stimulate efflux of AO) in a similar way to carbonyl cyanide m-chlorophenylhydrazone (CCCP), 2) increase the ATP-supported transvesicular membrane potential (i.e. quench oxonol V fluorescence) in contrast to CCCP and 3) enhance intravesicular uptake of [3H]-D-aspartic acid. These results suggest that positively charged, membrane impermeant amino alcohol species are generated within synaptic vesicles as they sequester protons. Cationic forms of these amino alcohols boost the transvesicular electrical potential which increases transmitter uptake into synaptic vesicles and facilitates enhancement of basal and evoked release of transmitter. Our data suggest a potential role for ethanolamine and related amino alcohols in the regulation of synaptic vesicle filling. These findings may also have relevance to neuropathophysiological states involving altered production of ethanolamine.