Ontogeny of pituitary adenylate cyclase activating polypeptide and its receptor mRNA in the mouse brain.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide which was first isolated from ovine hypothalamic tissue by screening for pituitary adenylate cyclase stimulating activity. Our previous data showed that radioimmunoassayable PACAP and PACAP-binding sites were detected in the whole rat brain as early as embryonic day 14(E14). In order to understand more precisely the developmental pattern of the synthesis of PACAP and its receptors in the brain, we studied the expression of PACAP and its receptor genes in the prenatal and postnatal mouse brain using RNase protection assay. The mRNAs for both PACAP and its receptor were detected as early as 9.5 days of gestation (E9.5) in the whole head of mouse embryos. The levels of PACAP mRNA in the brain increased during the prenatal period peaking at postnatal day 0 (P0). On the other hand, the levels of PACAP receptor mRNA gradually increased after E9.5. The levels sharply increased at P6 (479.0 +/- 82.5% of P0 levels), and then fell to the P3 levels at P10. These data together with our previous study on the ontogeny of PACAP immunoreactivity and its binding sites in the rat brain support the view that PACAP plays an important regulatory role in the development of brain.