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 the 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 adenosine nucleotides (ATP, App(NH)p) PACAP-27 increased TyrOH activity with a EC(50)of 100 nM. Since the PACAP-27 effect on TyrOH was abolished when homogenate or pellet of the nucleus accumbens were coincubated with CHAPS, the peptide effect appears to be receptor mediated. TyrOH activation produced by PACAP-27 increased in the presence of the phosphodiesterase inhibitor papaverine indicating the involvement of cAMP. The marked effect of the non-hydrolysable adenosine nucleotide App(NH)p also supports a cAMP-dependent TyrOH activation not related to ADP or an ADP-dependent mechanism. This report's data suggest that PACAP-27 activates TyrOH in the rat nucleus accumbens through receptor-mediated cAMP formation. The exact receptor type present in the nucleus accumbens has yet not been specified.
Moser
A
A
Neurochemical Research Group,Department of Neurology, Medical University of Lübeck, Lübeck, Germany. moser_a@neuro.mu-luebeck.de
Scholz
J
J
Gänsle
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007980:Levodopa / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000737:chemistry / Q000201:enzymology*; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000737:chemistry / Q000201:enzymology*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
C495403:Adcyap1 protein, rat; D015259:Dopamine Agents; D009479:Neuropeptides; D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000266:Adenylyl Imidodiphosphate; D007980:Levodopa; D000255:Adenosine Triphosphate; D010208:Papaverine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase