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Vesicular and conductive mechanisms of nucleotide release

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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.

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Notes

  1. The identity of the Golgi UDP-glucose/UMP translocator is not known, but UDP-N-acetylglucosamine/UMP translocators have been cloned and characterized [87].

  2. A recent study suggests that Panx2 forms octamers rather than hexamers [141].

Abbreviations

SLC:

Solute carrier

VNUT:

Vesicular nucleotide transporter

Panx:

Pannexin

Cx:

Connexin

siRNA:

Small interfering RNA

shRNA:

Short hairpin RNA

BAPTA:

1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid

DIDS:

4,4′-Diisothiocyanostilbene-2,2′-disulfonate

NBPP:

5-Nitro-2-(3-phenylpropylamino)benzoic acid

fMLP:

Formyl-Met-Leu-Phe

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Acknowledgments

We thank Lisa Brown for editorial assistance of the manuscript. Supported by National Institute of Health grant P01-HL034322.

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Lazarowski, E.R. Vesicular and conductive mechanisms of nucleotide release. Purinergic Signalling 8, 359–373 (2012). https://doi.org/10.1007/s11302-012-9304-9

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