SOMATOSTATIN AND PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) - 2 NEUROPEPTIDES POTENTIALLY INVOLVED IN THE DEVELOPMENT OF THE RAT CEREBELLUM

Somatostatin and pituitary adenylate cyclase-activating polypeptide (P ACAP) have been originally isolated from the ovine hypothalamus on the basis of their hypophysiotropic activities. There is now evidence tha t somatostatin and PACAP may play a role in the development of the cen tral nervous system, particularly in the cerebellum. High concentratio ns of somatostatin and somatostatin receptors have been detected in th e rat cerebellum during the first two postnatal weeks. Somatostatin bi nding sites are associated with a germinative matrix, the external gra nule cell layer, which generates the majority of the interneurons of t he cerebellum By using immature granule cells in primary culture, we c ould demonstrate that somatostatin binding sites are actually expresse d by neuroblasts and correspond to authentic receptors negatively coup led to adenylate cyclase. Concurrently, studies on the distribution of PACAP receptors in the immature rat cerebellum showed the presence of a high concentration of binding sites in the external granule cell la yer during the first two postnatal weeks. Pharmacological characteriza tion of these binding sites showed that they correspond to type I PACA P receptors positively coupled to adenylate cyclase. The concomitant a nd transient expression of somatostatin and PACAP receptors by cerebel lar neuroblasts in the external granule cell layer suggests that the t wo neuropeptides may be involved in the regulation of multiplication, migration and/or differentiation of neuroblasts. This hypothesis is al so supported by the actions of somatostatin and PACAP on various trans duction systems. In particular, the opposite effects of the two neurop eptides on adenylate cyclase activity suggest that somatostatin and PA CAP may exert antagonistic actions.