Dr. Cooper's project will attempt to elucidate the regulation of synaptic transmission. A factor has been isolated from brain, tentatively referred to as Substance B, which does not affect the evoked release of acetylcholine from nerve preparations, but which prevents the presynaptically modulated release. In both guinea pig ileum synaptosomes and intact preparation, Substance B reverses the release of acetylchone that is inhibited by muscarinic, purinergic and adrenergic agonists. In preliminary experimensts, Substance B also increases the EPSP in hippocampal slices and reverses the inhibition in firing rate produced by clonidine in locus coeruleus slices. This factor, currently being purified, is a low molecular weight hydrophilic compound that is present in heart and ileum as well as brain but is absent in liver and kidney. When the identity of this novel regulator factor has been established, he will determine its subcellular distribution, its biochemical and electrophysiological mechanism of action, and its effect on transmitters other than acetylcholine.
