Pituitary adenylate cyclase-activating polypeptide (PACAP-27) enhances tyrosine hydroxylase activity in the nucleus accumbens of the rat

Pituitary adenylate cyclase-activating polypeptide (PACAP-27) was incubated in a tyrosine hydroxylase (TyrOH) assay with a homogenate preparation of t he nucleus accumbens of the rat. TyrOH activity was determined in vitro by measuring the production of L-dopa with HPLC-ECD. Only in the presence of a denosine nucleotides (ATP, App(NH)p) PACAP-27 increased TyrOH activity with a EC50 of 100 nM. Since the PACAP-27 effect on TyrOH was abolished when ho mogenate or pellet of the nucleus accumbens were coincubated with CHAPS, th e peptide effect appears to be receptor mediated. TyrOH activation produced by PACAP-27 increased in the presence of the phosphodiesterase inhibitor p apaverine indicating the involvement of cAMP. The marked effect of the non- hydrolysable adenosine nucleotide App(NH)p also supports a cAMP-dependent T yrOH activation not related to ADP or an ADP-dependent mechanism. This repo rt's data suggest that PACAP-27 activates TyrOH in the rat nucleus accumben s through receptor-mediated cAMP formation. The exact receptor type present in the nucleus accumbens has yet not been specified. (C) 1999 Harcourt Pub lishers Ltd.