Extracellular adenine compounds within the cardiovascular system: Their source, metabolism and function

Abstract

This review covers a broad spectrum of issues related to extracellular adenine compounds within the cardiovascular system. Topics covered include: the cellular sources and detection of extracellular adenine compounds; the ecto-enzymes that mediate their metabolism; protein phosphorylation and function, and only briefly; purinoceptors and their functions. Extracellular nucleotides are generally not synthesized in biological extracellular environments. Why do some cell types store metabolically inert levels of ATP in storage granules that are released upon specific signals into the extracellular environment? Why are there a cadre of enzymes in many extracellular environments that can hydrolyze ATP to other bioactive molecules, such as ADP and adenosine, and kinases that transfer the gamma-phosphate of ATP to ecto-membrane/soluble proteins and protein phosphatases that reverse these reactions? A great deal of investigative attention has been focused on the characterization and functions of the purinergic cell surface receptors while less attention has been paid to the extracellular enzymes that catalyze a host of reactions with extracellular adenine compounds, such as protein phosphorylation and the functional outcomes of these reactions. This review is an attempt to garner more scientific interest in the potential roles extracellular adenine compounds play in the regulation of cell and cell-cell functions other than via purinergic signaling pathways as many of these reactions may play a role in diseased states and may serve as targets for new drug development. Keywords: Extracellular adenine compounds, Extracellular protein phosphorylation, Extracellular nucleotidases, Extracellular kinases, Extracellular enzymes