Journal article
Copper inhibits P2Y2-dependent Ca2+ signaling through the effects on thapsigargin-sensitive Ca2+ stores in HTC hepatoma cells
Biochemical and biophysical research communications, Vol.397(3), pp.493-498
07/02/2010
DOI: 10.1016/j.bbrc.2010.05.141
PMCID: PMC2899700
PMID: 20515656
Abstract
Purinergic P2Y
2
G-protein coupled receptors play a key role in the regulation of hepatic Ca
2+
signaling by extracellular ATP. The concentration of copper in serum is about 20 μM. Since copper accumulates in the liver in certain disease states, the purpose of these studies was to assess the effects of copper on P2Y
2
receptors in a model liver cell line. Exposure to a P2Y
2
agonist UTP increased [Ca
2+
]
i
by stimulating Ca
2+
release from thapsigargin-sensitive Ca
2+
stores. Pretreatment of HTC cells for several minutes with copper did not affect cell viability, but potently inhibited increases in [Ca
2+
]
i
evoked by UTP and thapsigargin. During this pretreatment, copper was not transported into the cytosol, and inhibited P2Y
2
receptors in a concentration-dependent manner with the
IC
50
of about 15 μM. These results suggest that copper inhibits P2Y
2
receptors through the effects on thapsigargin-sensitive Ca
2+
stores by acting from an extracellular side. Further experiments indicated that these effect of copper may lead to inhibition of regulatory volume decrease (RVD) evoked by hypotonic solution. Thus, copper may contribute to defective regulation of purinergic signaling and liver cell volume in diseases associated with the increased serum copper concentration.
Details
- Title: Subtitle
- Copper inhibits P2Y2-dependent Ca2+ signaling through the effects on thapsigargin-sensitive Ca2+ stores in HTC hepatoma cells
- Creators
- Svjetlana DolovcakShar L WaldropJ. Gregory FitzGordan Kilic
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.397(3), pp.493-498
- DOI
- 10.1016/j.bbrc.2010.05.141
- PMID
- 20515656
- PMCID
- PMC2899700
- NLM abbreviation
- Biochem Biophys Res Commun
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Grant note
- name: National Institute of Health, award: DK46082
- Language
- English
- Date published
- 07/02/2010
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094359502771
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