Effects of Active Fragments AgRP 83-132 and 25-51 on Dopamine Biosynthesis in the Brain

Experiments using C57BL/6J mice 3 h after administration of agouti gene-related peptide (AgRP) fragments 83-132 and 25-51 into the midbrain identified dose-dependent inhibitory effects on dopaminergic neurons. Staining of midbrain sections using an immunohistochemical method with specific antibodies showed that fragment AgRP 83-132 induced significant decreases in tyrosine hydroxylase phosphorylated at serine-40 and serine-31 in neurons. Administration of AgRP fragment 25-51 produced a significant decrease only in tyrosine hydroxylase phosphorylated at serine-31. Studies using high-performance liquid chromatography demonstrated significant decreases in dopamine levels in the striatum after administration of both fragments. This article discusses the mechanisms inducing changes in tyrosine hydroxylase activity in midbrain structures and the actions of AgRP 25-51 via G-protein-independent pathways and particularly the role of the ERK1/2 module of the MAPK kinase cascade.