Chromogranin A inhibits dopamine release from rat striatal slices

Chromogranin A (CGA), a prohormone and a protein component of endocrine and neural secretory granules, neuritic plaques in Alzheimer's disease and Lewy bodies in Parkinson's disease, inhibited the release of dopamine (DA) from perfused rat striatal slices. Dopamine release was stimulated by a pulse of high potassium (40 mM) medium introduced at 20 minutes (K1) and 55 minutes (K2) following equilibration. The ratio of K2/K1 was 0.80 ± 0.04 in control tissues, but fell significantly to 0.26 ± 0.08 when 100 nM purified CGA was added prior to the second potassium pulse. This reduction in DA release was equivalent to that seen when calcium was excluded from the buffer (0.19 ± 0.05). Pancreastatin, a centrally active peptide product of CGA, had no effect on stimulated DA release (0.77 ± 0.06), although it, as well as the other treatments, did reduce basal DA release. It is likely that the parent molecule itself, CGA, or an as yet unidentified product is responsible for inhibition of K-stimulated striatal DA release.