PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation

Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL cell neoplasia is unknown. Methods and results: ECL cell transformation was induced in the Mastomys using 16 wk H 2 receptor blockade of acid inhibition. Examination of the epithelial fundic mucosa demonstrated that PACAP-immunoreactivity significantly increased in the tumor mucosa compared to the naı̈ve stomach, and was associated with ECL cells. Naı̈ve and tumor ECL cells were then purified (∼95%) from Mastomys and the presence of all three PACAP/VPAC receptor subtypes was demonstrated by polymerase chain-reaction amplification. Thereafter, cells were maintained in short-term (48 h) primary cultures. PACAP significantly ( p