Ontogeny of zeta (ζ), the opioid growth factor receptor, in the rat brain

Opioid growth factor (OGF), [Met⁵]enkephalin, serves as an inhibitory influence on the developing nervous system and is especially targeted to cell proliferative events. OGF interacts with the zeta (ζ) opioid receptor to perform its function. Using [³H]-[Met⁵]enkephalin, the ontogeny of the ζ receptor in the whole brain and cerebellum of rats was explored. Specific and saturable binding was recorded at the earliest time sampled, prenatal day 15 (E15). In the whole brain, binding capacity (B_max) was two-fold greater at E15 than at E18 adn E20. The quantity of ζ receptor appeared to increase in the first postnatal week, reaching a maximum on postnatal day 8. Binding decreased the remainder of the 2nd week and between postnatal days 15 and 25 binding was no longer recorded. In the cerebellum, binding capacity increased from E20 to the 2nd postnatal week, reaching a maximum on postnatal days 8-10. The B_max receptor decreased precipitously on postnatal day 11, being 5.4-fold lower than on postnatal day 10. Between postnatal days 21 and 30, no binding was observed. The binding affinities of the whole brain and cerebellum were 2.3 and 2.7 nM, respectively, and no differences between ages could be observed. The binding affinities of the whole brain and cerebellum postnatal day 6 increased body weight, the B_max of the ζ receptor in the whole brain and cerebellum (but not the K_d), and increased the number of layers of germinal cells in the cerebellum. These results define the temporal expression of the ζ receptor in the rat brain, as well as some regulatory properties, and support the concept that the ζ opioid receptor is primarily related to the proliferation of cells in the nervous system.