Given the widespread importance of purinergic receptor-evoked signaling, understanding how ATP and other nucleotides are released from cells in a regulated manner is an essential physiological question. Nonlytic release of ATP, UTP, UDP-glucose, and other nucleotides occurs in all cell types and tissues via both constitutive mechanisms, that is, in the absence of external stimuli, and to a greater extent in response to biochemical or mechanical/physical stimuli. However, a molecular understanding of the processes regulating nucleotide release has only recently begun to emerge. It is generally accepted that nucleotide release occurs in two different scenarios, exocytotic release from the secretory pathway or via conductive/transport mechanisms, and a critical review of our current understanding of these mechanisms is presented in this chapter.
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