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 neuri te outgrowth of Neuro-2a cells in a naloxone-eversible manner. The sti mulating effect of beta-casomorphin-5 was observed even at picomolar c oncentrations. The selective mu-agonist, (D-Ala(2), N-Me-Phe(4), Gly(5 )-ol)-enkephalin (DAMGO) exhibited the similar stimulating effect only at micromolar concentrations. On the other hand, (D-Pen(2,5))-enkepha lin (DPDPE) (a delta-agonist), U-50,488 (a kappa-agonist), and endogen ous opioid peptides, such as enkephalins and dynorphin A (1-13), showe d no such stimulating effect. These results suggest that the neurite o utgrowth-stimulating action of beta-casomorphin-5 may be mediated via a receptor which has mu-like characteristics and high sensitivity to b eta-casomorphin-5, and that beta-casomorphins may play a role as a neu rite elongation factor during the suckling period. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.