The neuropeptide somatostatin has been found to be abundant in numerou
s developing regions within the central nervous system. In order to un
derstand the role of somatostatin in development, effects of exposure
to the neuropeptide were studied in PC12 cells, a well characterized m
odel of neuronal differentiation. Somatostatin increased neurite outgr
owth after 2 days in culture and enhanced neurite outgrowth after nerv
e growth factor (NGF) exposure. This effect was inhibited by somatosta
tin antibody and pertussis toxin. Somatostatin had no effect on NGF bi
nding or internalization but did cause a decrease in cAMP levels durin
g the time of maximal stimulation of neurite outgrowth. In a protein k
inase A-deficient cell line (A126-1B2), somatostatin had no effect on
neurite outgrowth. These results indicate that somatostatin may functi
on as a differentiation factor in developing systems through inhibitio
n of cAMP synthesis.