Differences in the ways sympathetic neurons and endocrine cells process, store, and secrete exogenous neuropeptides and peptide-processing enzymes

Most neurons store peptides in large dense core vesicles (LDCVs) and releas e the neuropeptides in a regulated manner. Although LDCVs have been studied in endocrine cells, less is known about these storage organelles in neuron s. In this study we use the endogenous peptide NPY (neuropeptide Y) and the endogenous peptide-processing enzyme PAM (peptidylglycine alpha-amidating monooxygenase) as tools to study the peptidergic system in cultured neurons from the superior cervical ganglion (SCG). Once mature, SCG neurons devote as much of their biosynthetic capabilities to neurotransmitter production as endocrine cells devote to hormone production. Unlike pituitary and atriu m, SCG neurons cleave almost all of the bifunctional PAM protein they produ ce into soluble monofunctional enzymes. Very little PAM or NPY is secreted under basal conditions, and the addition of secretagogue dramatically stimu lates the secretion of PAM and NPY to a similar extent. Although endocrine cells typically package "foreign" secretory products together with endogeno us products, pro-opiomelanocortin- and PAM-derived products encoded by aden ovirus in large part were excluded from the LDCVs of SCG neurons. When expr essed in corticotrope tumor cells and primary anterior pituitary cultures, the same virally encoded products were metabolized normally. The difference s that were observed could reflect differences in the properties of neurona l and endocrine peptidergic systems or differences in the ability of neuron s and endocrine cells to express viral transcripts.