Anaphylatoxins C3a and C5a are pharmacologically active peptides derived from the third and fifth components of serum complement. When administered focally to the rat hypothalamus, they mimic the neurotransmitters dopamine and norepinephrine in their respective abilities to modify standard behavioral tests. There are specific binding sites for both peptides on fresh brain slices and for C3a on synaptosome fractions (nerve terminal fractions in vitro). C5a has been shown to stimulate the release of both dopamine and norepinephrine from synaptosomes. Preliminary data obtained by high performance liquid chromatography indicate that C3a releases dopamine from synaptosomes of the striatal region of the forebrain. Dr. William's data are the first report of activities of the anaphylatoxins in the central nervous system. Further study of these phenomena may reveal their possible modulatory function in the brain. There are two main objectives in Dr. William's proposed studies. The first objective is to characterize the locations and mechanisms of neurotransmitter releasing activity in the brain. The release of neurotransmitter substances in vitro in the presence of blockers for calcium channels, GTP binding proteins and autoreceptors. The second objective is to associate the brain binding sites with specific nerve terminal types by immunocytochemistry and transmission electron microscopy.
