Vesicular and conductive mechanisms of nucleotide release

Abstract

Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

Role of vesicular nucleotide transporter VNUT (SLC17A9) in release of ATP from AR42J cells and mouse pancreatic acinar cells

“…Also in biliary epithelial cells, hypotonic stress caused ATP release by VNUT-dependent exocytosis [11]. Nevertheless, there are different forms of mechanical stress, and most cells tested react with ATP release, and there are probably several paths for ATP release, and some may depend on intracellular Ca 2+ stores [2,3]. In any case, we show that mechanical release and basal release are not associated with the inducible zymogen granule and VNUT expression and therefore ZG exocytosis towards lumen (Fig.…”

“…ATP is released from most cells, and the release mechanism is currently an intensive research field, where the focus is on identifying whether ATP is released via ion channels/ transporters, pannexin or connexins, or via vesicular transport [2,3]. In the exocrine pancreas, it has been well documented that acini release ATP in response to physiological signals, such as cholinergic agonists, cholecystokinin, and neurotensin [4][5][6].…”

P2X receptors regulate adenosine diphosphate release from hepatic cells

“…Nucleotides are released from the cell through connexin hemichannels and pannexin channels and through exocytotic secretory pathways [19]. The channels are known to mediate a conductive release of ATP and UTP, while the vesicular nucleotide transporter (VNUT) transports nucleotides into dense-core granules and vesicles for Ca 2+ -regulated exocytosis.…”

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

“…Two main pathways are responsible for this regulated release of ATP: exocytotic and conductive (for review, see [13]). The first mechanism involves 1) Golgi-derived secretory vesicles mobilized by constitutive exocytotic pathways utilized by protein secretion, and 2) specialized secretory granules that actively accumulate ATP which is released during Ca 2+ -dependent regulated exocytosis.…”