Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a)

We studied the effect of beta-casomorphin-5 (mu-acting opioid peptides derived from milk protein beta-casein) on neurite outgrowth of mouse neuroblastoma cell line, Neuro-2a. Beta-casomorphin-5 stimulated neurite outgrowth of Neuro-2a cells in a naloxone-reversible manner. The stimulating effect of beta-casomorphin-5 was observed even at picomolar concentrations. The selective mu-agonist, (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) exhibited the similar stimulating effect only at micromolar concentrations. On the other hand, (D-Pen(2,5))-enkephalin (DPDPE) (a delta-agonist), U-50,488 (a kappa-agonist), and endogenous opioid peptides, such as enkephalins and dynorphin A (1-13), showed no such stimulating effect. These results suggest that the neurite outgrowth-stimulating action of beta-casomorphin-5 may be mediated via a receptor which has mu-like characteristics and high sensitivity to beta-casomorphin-5, and that beta-casomorphins may play a role as a neurite elongation factor during the suckling period.