Journal article
Evidence for sustained ATP release from liver cells that is not mediated by vesicular exocytosis
Purinergic signalling, Vol.7(4), pp.435-446
12/2011
DOI: 10.1007/s11302-011-9240-0
PMCID: PMC3224646
PMID: 21630025
Abstract
Extracellular ATP regulates many important cellular functions in the liver by stimulating purinergic receptors. Recent studies have shown that rapid exocytosis of ATP-enriched vesicles contributes to ATP release from liver cells. However, this rapid ATP release is transient, and ceases in ~30 s after the exposure to hypotonic solution. The purpose of these studies was to assess the role of vesicular exocytosis in sustained ATP release. An exposure to hypotonic solution evoked sustained ATP release that persisted for more than 15 min after the exposure. Using FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide) fluorescence to measure exocytosis, we found that hypotonic solution stimulated a transient increase in FM1-43 fluorescence that lasted ~2 min. Notably, the rate of FM1-43 fluorescence and the magnitude of ATP release were not correlated, indicating that vesicular exocytosis may not mediate sustained ATP release from liver cells. Interestingly, mefloquine potently inhibited sustained ATP release, but did not inhibit an increase in FM1-43 fluorescence evoked by hypotonic solution. Consistent with these findings, when exocytosis of ATP-enriched vesicles was specifically stimulated by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), mefloquine failed to inhibit ATP release evoked by NPPB. Thus, mefloquine can pharmacologically dissociate sustained ATP release and vesicular exocytosis. These results suggest that a distinct mefloquine-sensitive membrane ATP transport may contribute to sustained ATP release from liver cells. This novel mechanism of membrane ATP transport may play an important role in the regulation of purinergic signaling in liver cells.
Details
- Title: Subtitle
- Evidence for sustained ATP release from liver cells that is not mediated by vesicular exocytosis
- Creators
- Svjetlana Dolovcak - Department of Internal Medicine University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas TX 75390-9151 USAShar Waldrop - Department of Internal Medicine University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas TX 75390-9151 USAFeng Xiao - Department of Internal Medicine University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas TX 75390-9151 USAGordan Kilic - Department of Internal Medicine University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas TX 75390-9151 USA
- Resource Type
- Journal article
- Publication Details
- Purinergic signalling, Vol.7(4), pp.435-446
- Publisher
- Springer Netherlands
- DOI
- 10.1007/s11302-011-9240-0
- PMID
- 21630025
- PMCID
- PMC3224646
- ISSN
- 1573-9538
- eISSN
- 1573-9546
- Language
- English
- Date published
- 12/2011
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094572602771
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