PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE STIMULATES NEURITE GROWTH IN PC12 CELLS

The ability of PACAP-38 to stimulate morphological development was stu died using rat pheochromocytoma PC12 cells. PACAP-38 produced concentr ation-dependent increases in percentage of cells exhibiting neurite ex tension. Similar increases were produced by forskolin (28 +/- 2% at 96 h) and 8-bromo cAMP (30 +/- 2%). Vasoactive intestinal peptide and al pha-calcitonin gene-related peptide were without effect. PACAP-38 prod uced significant increases in PC12 cell cAMP content and inositol phos phate turnover. Intracellular [Ca2+] increased from 169 +/- 14 nM to 5 60 +/- 58 nM in response to 1 mu M PACAP-38. PACAP-stimulated neurite outgrowth was abolished by R(p)cAMPS, an inhibitor of cAMP-dependent k inases but was unaffected by the protein kinase C antagonist 117.