ABSTRACT
Peripheral dopamine (DA) does not come from the brain but, rather, originates from both neuronal and nonneuronal tissues, as well as from some food items. Although the biosynthetic pathways of brain and peripheral DA are similar, they differ primarily in the mechanisms that govern the release, reuptake, and metabolic inactivation of DA. A unique aspect of peripheral DA is its inactivation by sulfoconjugation, which generates biologically inactive DA-sulfate (DA-S) with a prolonged serum half-life. Tissues that express arylsulfatase A (ARSA) can convert DA-S to free DA. The ability of normal and malignant cells to utilize DA-S is paramount to the pathophysiology of peripheral DA. Outside the brain, DA functions primarily as a local paracrine messenger. The peripheral actions of DA are executed via variable levels of expression of the five DARs in various organs and systems, including the cardiopulmonary, digestive, metabolic, hematopoietic, immune, dermal, and reproductive systems.
