ONTOGENY OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) RECEPTORS IN THE RAT CEREBELLUM - A QUANTITATIVE AUTORADIOGRAPHIC STUDY

Pituitary adenylate cyclase-activating polypeptide and PACAP receptors are both present in the rat cerebellar cortex, suggesting that PACAP may play an important role in the cerebellum. In the present study, th e variation of the concentration of PACAP binding sites in the rat cer ebellum was investigated during postnatal development by means of quan titative autoradiography, using [I-125]PACAP27 as a radioligand. In th e external granule cell layer and the medulla, the density of PACAP bi nding sites was high at birth, markedly decreased from postnatal day 8 (P8) to P25 and finally vanished at the end of the third postnatal we ek. In the internal granule cell layer and molecular layer, PACAP bind ing sites were first detected at P8. In the internal granule cell laye r, the density of binding sites slightly decreased during development but remained elevated in adults. Conversely, in the molecular layer, P ACAP binding sites rapidly decreased during the second and third postn atal weeks and virtually disappeared after P25. In all four layers of the cerebellar cortex, the autoradiographic labeling was displaced by PACAP27 (IC50 close to 10(-8) M), but was not affected by VIP. No sign ificant changes in IC50 and Hill coefficient were noticed in the vario us layers throughout development. The present study shows that all fou r layers of the cerebellar cortex express PACAP binding sites during d evelopment. The evolution of the receptor concentration exhibited diff erential profiles in the various layers but the specificity characteri stics of the recognition sites were identical in all four structures. The intense and transient expression of PACAP binding sites in the ext ernal granule cell layer, a germinative matrix which generates the maj ority of cerebellar interneurons, supports the concept that PACAP may play important functions during histogenesis of the cerebellum.