ABSTRACT
This chapter provides an overview of the fundamental processes that govern dopamine (DA) homeostasis: synthesis, metabolism, release, reuptake, and storage. At any given time, DA homeostasis is determined by multiple complementary processes that are tightly regulated and well-coordinated. Catecholamine biosynthesis involves several sequential enzymatic reactions, with tyrosine hydroxylase (TH) serving as the rate-limiting step. Metabolic degradation is carried out primarily by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT), with additional glucuronidation and sulfation reactions. Within the producing cells, DA is stored in secretory vesicles whose main function is to protect it from degradation and enable its regulated release by a calcium-dependent exocytosis. Several types of transporters-the dopamine transporter (DAT), the vesicular monoamine transporters (VMATs), and organic cation transporters (OCTs)-are involved with the termination of the action of released DA through reuptake mechanisms and repackaging into the secretory granules. The different cytoarchitecture of DA within the "closed system" of the brain and the "open system" of the periphery necessitates several modifications of the fundamental processes of synthesis, metabolism, storage, transport and release of peripheral DA.
