Somatostatin enhances neurite outgrowth in PC12 cells.

The rat pheochromocytoma cell line PC12 forms neurites in response to nerve growth factor (NGF), and it was also reported to extend processes in the presence of somatostatin (somatotropin release-inhibiting factor, SRIF), a neuroactive peptide that seems to act as a morphogenetic factor in the developing nervous system. In the present study, we re-evaluated the effects of SRIF on PC12 cell differentiation. Our results indicate that SRIF alone is ineffective in promoting neurite outgrowth. Instead, SRIF or its analogue, octreotide (a SRIF agonist on the receptor subtypes 2, 3 and 5), potentiates neurite extension induced by NGF. These results suggest that SRIF enhances neurite formation in PC12 cells without directly promoting neurite outgrowth. SRIF potentiation of NGF-induced neurite outgrowth persists at least in part in the presence of pertussis toxin (PTX), suggesting the involvement of PTX-insensitive G-proteins. In addition, protein kinase-dependent pathways are likely to mediate SRIF effects on NGF-induced differentiation.