VENTRAL MESENCEPHALIC AND CORTICAL TRANSPLANTS INTO THE RAT STRIATUM DISPLAY ENHANCED ACTIVITY FOR NEUTRAL ENDOPEPTIDASE 24.11 (ENKEPHALINASE CALLA)

A role for neutral endopeptidase 24.11 (NEP) in growth and development is supported by the demonstration that NEP hydrolyses and inactivates a number of peptide growth factors including atrial natriuretic pepti de, endothelins, bombesin-like peptides, and opioid peptides, includin g the enkephalins. In the present study, suspensions of cells obtained from the ventral mesencephalon or cortex of rat embryos (ED14) were i mplanted into the striatum of the adult rat brain. Three to 15 weeks a fter transplantation the relative distribution of NEP-positive cellula r elements was visualized histochemically. NEP staining in the transpl ants consistently appeared before NEP staining in the surrounding host striatum supporting a relative increase in NEP activity in the transp lants. The NEP staining richly visualized cells of varying size and mo rphology which lacked the normal organization of the host striatum. Th e histochemical staining in the transplants and the surrounding host t issue was completely blocked by a 100 nM concentration of the selectiv e NEP inhibitors phosphoramidon or JHF-26, supporting the exclusive lo calization of NEP by this method. NEP localization in the embryonic (E D14) cortex and ventral mesencephalon was also confirmed, suggesting o ne possible origin for the NEP-positive cells visualized in the transp lants. Fluorescent double-labeling studies for NEP and glial fibrillar y acidic protein (GFAP) or transforming growth factor alpha precursor (TGFalphap) revealed the presence of rich glial labeling within the tr ansplants for both GFAP and TGFap. NEP-labeled cells in the transplant s were closely associated with glial elements, however, only occasiona l glial elements in the transplants stained for NEP; supporting a non- astrocytic localization for the NEP in the transplants. The marked enh ancement of NEP staining in the transplants may have significance for controlling the rate or pattern of growth of the transplanted cells th rough inactivation of peptide growth factors produced by, or in respon se to, the transplants.