NMDA RECEPTOR ACTIVATION ENHANCES THE RELEASE OF A CHOLINERGIC DIFFERENTIATION PEPTIDE (HCNP) FROM HIPPOCAMPAL-NEURONS IN-VITRO

Hippocampal cholinergic neurostimulating peptide (HCNP) is a novel und ecapeptide purified from the hippocampus of young rats. The peptide st imulates cholinergic phenotype development in the rat medial septal nu cleus in vitro. Here, we have focused on the mechanism of release of t he peptide from the hippocampus, by applying tissue culture techniques . Quantitation of HCNP in the culture supernatant after chemical stimu lation was carried out by RTA, and by a combination of HPLC and RTA. W e found that the N-methyl-D-aspartate (NMDA) receptor specifically med iates release of the deacetylated form of HCNP from the culture. Our r esults suggest that during the early development of hippocampal neuron s, the peptide is released by NMDA receptor activation, and that it ma y be involved in mediating the effect of activity-dependent cues on de veloping septal cholinergic neurons. (C) 1998 Elsevier Science B.V.