Differential release of amino acids, neuropeptides, and catecholamines from isolated nerve terminals

We have investigated transmitter release from small and large dense-core vesicles in nerve terminals isolated from guinea pig hippocampus. Small vesicles are found in clusters near the active zone, and large dense-core vesicles are located at ectopic sites. The abilities of Ca 2+ channel activation and uniform elevation of Ca 2+ concentration (with ionophores) to evoke secretion of representative amino acids, catecholamines, and neuropeptides were compared. For a given increase in Ca 2+ concentration, ionophore was less effective than Ca 2+ channel activation in releasing amino acids, but not in releasing cholecystokinin-8. Titration of the average Ca 2+ concentration showed that the Ca 2+ affinity for cholecystokinin-8 secretion was higher than that for amino acids. Catecholamine release showed intermediate behavior. It is concluded that neuropeptide release is triggered by small elevations in the Ca 2+ concentration in the bulk cytoplasm, whereas secretion of amino acids requires higher elevations, as produced in the vicinity of Ca 2+ channels.