Developmental changes of pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor in the rat brain.

The developmental changes of PACAP and its receptor in the rat brain were investigated. The levels of PACAP and its receptor in the brain were determined by radioimmunoassay (RIA) and radioreceptor assay, respectively. The [125I]PACAP27 binding to the whole brain membrane preparations from embryonic day (E)18 rats was specific, rapid, and temperature dependent. Scatchard plot analysis revealed only a single class of receptor with Kd for PACAP27 = 1.015 +/- 0.049 nM, Kd for PACAP38 = 0.105 +/- 0.003 nM, and Bmax for both ligands = 8.64 +/- 1.29 pmol/mg protein. The Kd for PACAP38 was significantly lower than that for PACAP27. The binding site for PACAP was detected as early as E14. The Bmax for PACAP gradually increased throughout development to reach a plateau between 1 and 4 months old (MO). The content of PACAP38 in the whole brain was detected by RIA as early as E14. The concentration of PACAP38 in the whole brain, hippocampus, neocortex, and cerebellum gradually increased throughout the pre- and postnatal periods to reach a peak at 1 MO and then tended to decrease between 1 and 4 MO. On the other hand, PACAP38 concentration in the diencephalon rapidly increased between E18 and the birth (P0), and then increased more slowly throughout the postnatal period to reach a peak at 1 MO. In view of a neurotrophic activity of PACAP, these findings may support the notion that PACAP plays a regulatory role in neuronal growth and development.