Comparative distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites and PACAP receptor mRNAs in the rat brain during development.

The distribution and density of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites as well as PACAP-specific receptor 1 (PAC1-R), vasoactive intestinal polypeptide/PACAP receptor 1 (VPAC1-R), and VPAC2-R mRNAs have been investigated in the rat brain from embryonic day 14 (E14) to postnatal day 8 (P8). Significant numbers of binding sites for the radioiodinated, 27-amino-acid form of PACAP were detected as early as E14 in the neuroepithelia of the metencephalon and the myelencephalon. From E14 to E21, the density of binding sites in the germinative areas increased by 3- to 5-fold. From birth to P12, the density of binding sites gradually declined in all neuroepithelia except in the external granule cell layer of the cerebellum, where the level of binding sites remained high during the first postnatal weeks. Only low to moderate densities of PACAP binding sites were found in regions other than the germinative areas, with the exception of the internal granule cell layer of the cerebellum, which contained a high density of sites. The localization of PACAP receptor mRNAs was investigated by in situ hybridization using [(35)S] uridine triphosphate-specific riboprobes. The evolution of the distribution of PAC1-R and VPAC1-R mRNAs was very similar to that of PACAP binding sites, the concentration of VPAC1-R mRNA being much lower than that of PAC1-R mRNA. In contrast, intense expression of VPAC2-R mRNA was observed in brain regions other than germinative areas, such as the suprachiasmatic, ventral thalamic, and dorsolateral geniculate nuclei. The discrete localization of PACAP binding sites as well as PAC1-R and VPAC1-R mRNAs in neuroepithelia during embryonic life and postnatal development strongly suggests that PACAP, acting through PAC1-R and/or VPAC1-R, may play a crucial role in the regulation of neurogenesis in the rat brain.