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.