Regulation Of Pre- And Postsynaptic Protein Phosphorylation By Dopamine D2 Receptors

Dopamine D2-type receptors are coupled to G(i/o) proteins, which inhibit adenylyl cyclase, the enzyme responsible for the synthesis of 3',5' -cyclic monophosphate (cAMP). Therefore, a considerable proportion of the effects produced on protein phosphorylation by pharmacological manipulations of these receptors is mediated by changes in the activity of cAMP-dependent protein kinase. Studies performed in the striatum, a brain region particularly enriched in D2-type receptors, have led to the identification of several downstream target phosphoproteins regulated by D2-type receptor agonists and antagonists. This chapter provides a short introductory summary of the mechanisms involved in such regulations and describes two standard methodologies, Western blotting and immunohistochemistry, which can be employed to investigate changes in the state of phosphorylation of D2-type receptor targets localized at presynaptic and postsynaptic level.