Basal release of ATP: an autocrine-paracrine mechanism for cell regulation

Abstract

Cells release adenosine triphosphate (ATP), which activates plasma membrane-localized P2X and P2Y receptors and thereby modulates cellular function in an autocrine or paracrine manner. Release of ATP and the subsequent activation of P2 receptors help establish the basal level of activation (sometimes termed "the set point") for signal transduction pathways and regulate a wide array of responses that include tissue blood flow, ion transport, cell volume regulation, neuronal signaling, and host-pathogen interactions. Basal release and autocrine or paracrine responses to ATP are multifunctional, evolutionarily conserved, and provide an economical means for the modulation of cell, tissue, and organismal biology.

Fig. 1. Autocrine and paracrine actions of extracellular ATP

Cells release ATP into the extracellular space where it can activate P2X and P2Y receptors, or, after hydrolysis of ATP by ecto-ATPases to generate adenosine, P1 receptors on the cells that released ATP (autocrine signaling) or on neighboring cells (paracrine signaling).

Fig. 2. Control of blood flow by autocrine and paracrine ATP signaling

Extracellular ATP modulates vascular smooth muscle cell tone by activating P2Y₁₃ receptors on the lumenal membrane of endothelial cells, which in turn leads to the production of nitric oxide (NO), prostaglandins (PGs), and endothelium-derived hyperpolarizing factor (EDHF). During oxygen deprivation, endothelial cells and erythrocytes release increased amounts of ATP, which leads to the increased activation of P2Y₁₃ and vasodilation.