REGULATION BY INSULIN OF A UNIQUE NEURONAL CA2+ POOL AND OF NEUROPEPTIDE SECRETION

The insulin receptor is a tyrosine kinase receptor that is found in ma mmalian brain(1) and at high concentrations in the bag cell neurons of Aplysia(2). We show here that insulin causes an acute rise in intrace llular Ca2+ concentration ([Ca2+](i)) in these neurons and triggers re lease of neuropeptide. The insulin-sensitive intracellular Ca2+ pool d iffers pharmacologically from previously described Ca2+ stores that ar e sensitive to inositol trisphosphate and from mitochondrial Ca2+ stor es(3-7). Insulin, but not thapsigargin, stimulates Ca2+ release at the distal tips of neurites, the presumed site of neuropeptide secretion( 8,9). The effects of insulin on intracellular Ca2+ release and neurope ptide secretion occur without triggering spontaneous action potentials . The insulin-sensitive rise in [Ca2+](i) moves into the distal tips o f neurites after exposure to a cyclic AMP analogue, a treatment that c auses a similar translocation of neuronal vesicles(10-12). Our data in dicate that Ca2+ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide i n the absence of neuronal discharge.