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

The distribution and density of pituitary adenylate cyclase-activating poly peptide (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 radio iodinated, 27-amino-acid form of PACAP were detected as early as E14 in the neuroepithelia of the metencephalon and the myelencephalon. From E14 to E2 1, 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 cer ebellum, where the level of binding sites remained high during the first po stnatal weeks. Only low to moderate densities of PACAP binding sites were f ound in regions other than the germinative areas, with the exception of the internal granule cell layer of the cerebellum, which contained a high dens ity of sites. The localization of PACAP receptor mRNAs was investigated by in situ hybridization using [S-35] uridine triphosphate-specific riboprobes . The evolution of the distribution of PAC1-R and VPAC1-R mRNAs was very si milar to that of PACAP binding sites, the concentration of VPAC1-R mRNA bei ng 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, su ch as the suprachiasmatic, ventral thalamic, and dorsolateral geniculate nu clei. The discrete localization of PACAP binding sites as well as PAC1-R an d VPAC1-R mRNAs in neuroepithelia during embryonic life and postnatal devel opment 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. (C) 2000 Wiley-Liss, Inc.