Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in... Cisplatin-based concomitant chemoradiotherapy is considered as the standard treatment for locally advanced nasopharyngeal carcinoma patients. However, the curative efficacy of cisplatin-based chemotherapy is limited because of the occurrence of cisplatin resistance. Some researches indicate that activating the volume-sensitive Cl− channel might be a new strategy for the reduction of cisplatin resistance. However, little is known about the activation pathway of the Cl− channels activated by cisplatin. In this study, the cisplatin-activated chloride current was investigated using the whole cell patch-clamp technique in the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z cells), and the activation pathway of the current was also discussed. The results showed that extracellular application of cisplatin activated a Cl− current, showing the properties of significant outward rectification, intracellular ATP dependency, and a selectivity sequence of I− > Br− > Cl− > gluconate, and being inhibited by the Cl− channel inhibitors tamoxifen and extracellular ATP. These characteristics are similar to those of the volume-sensitive Cl− current in CNE-2Z cells, indicating that cisplatin induces the Cl− current by activating the volume-sensitive like chloride channel. The cisplatin-activated current was blocked by suramin (a wide-spectrum purinergic antagonist) and RB2 (a relatively selective P2Y antagonist). In addition, the current was depressed by extracellular application of apyrase. The apoptotic volume decrease induced by cisplatin was also attenuated by RB2. P2Y receptors were expressed in CNE-2Z cells. These results suggest that cisplatin can induce a Cl− current by activating volume-sensitive like Cl− channels through the P2Y purinoceptor pathway. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

Loading next page...
 
/lp/springer_journal/cisplatin-activates-volume-sensitive-like-chloride-channels-via-JVJXH19OFW
Publisher
Springer US
Copyright
Copyright © 2014 by Springer Science+Business Media New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-014-9724-2
Publisher site
See Article on Publisher Site

Abstract

Cisplatin-based concomitant chemoradiotherapy is considered as the standard treatment for locally advanced nasopharyngeal carcinoma patients. However, the curative efficacy of cisplatin-based chemotherapy is limited because of the occurrence of cisplatin resistance. Some researches indicate that activating the volume-sensitive Cl− channel might be a new strategy for the reduction of cisplatin resistance. However, little is known about the activation pathway of the Cl− channels activated by cisplatin. In this study, the cisplatin-activated chloride current was investigated using the whole cell patch-clamp technique in the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z cells), and the activation pathway of the current was also discussed. The results showed that extracellular application of cisplatin activated a Cl− current, showing the properties of significant outward rectification, intracellular ATP dependency, and a selectivity sequence of I− > Br− > Cl− > gluconate, and being inhibited by the Cl− channel inhibitors tamoxifen and extracellular ATP. These characteristics are similar to those of the volume-sensitive Cl− current in CNE-2Z cells, indicating that cisplatin induces the Cl− current by activating the volume-sensitive like chloride channel. The cisplatin-activated current was blocked by suramin (a wide-spectrum purinergic antagonist) and RB2 (a relatively selective P2Y antagonist). In addition, the current was depressed by extracellular application of apyrase. The apoptotic volume decrease induced by cisplatin was also attenuated by RB2. P2Y receptors were expressed in CNE-2Z cells. These results suggest that cisplatin can induce a Cl− current by activating volume-sensitive like Cl− channels through the P2Y purinoceptor pathway.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Sep 19, 2014

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off