Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats

Background: Adenosine 5′-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve...

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Main Authors: Yoshizo Matsuka, Takeshi Ono, Hirotate Iwase, Somsak Mitrirattanakul, Kevin S. Omoto, Ting Cho, Yan Yan N. Lam, Bradley Snyder, Igor Spigelman
Other Authors: University of California, Los Angeles
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Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/18794
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spelling th-mahidol.187942018-07-12T09:49:24Z Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats Yoshizo Matsuka Takeshi Ono Hirotate Iwase Somsak Mitrirattanakul Kevin S. Omoto Ting Cho Yan Yan N. Lam Bradley Snyder Igor Spigelman University of California, Los Angeles Okayama University Japan Ground Self Defense Force Medical School Mahidol University Biochemistry, Genetics and Molecular Biology Medicine Neuroscience Background: Adenosine 5′-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE). Results: After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15-21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N6-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O2consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O2at a higher rate than control or contralateral DRG. Conclusion: These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation. © 2008 Matsuka et al; licensee BioMed Central Ltd. 2018-07-12T02:15:58Z 2018-07-12T02:15:58Z 2008-12-24 Article Molecular Pain. Vol.4, (2008) 10.1186/1744-8069-4-66 17448069 2-s2.0-59349112493 https://repository.li.mahidol.ac.th/handle/123456789/18794 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=59349112493&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
Neuroscience
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
Neuroscience
Yoshizo Matsuka
Takeshi Ono
Hirotate Iwase
Somsak Mitrirattanakul
Kevin S. Omoto
Ting Cho
Yan Yan N. Lam
Bradley Snyder
Igor Spigelman
Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
description Background: Adenosine 5′-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE). Results: After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15-21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N6-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O2consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O2at a higher rate than control or contralateral DRG. Conclusion: These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation. © 2008 Matsuka et al; licensee BioMed Central Ltd.
author2 University of California, Los Angeles
author_facet University of California, Los Angeles
Yoshizo Matsuka
Takeshi Ono
Hirotate Iwase
Somsak Mitrirattanakul
Kevin S. Omoto
Ting Cho
Yan Yan N. Lam
Bradley Snyder
Igor Spigelman
format Article
author Yoshizo Matsuka
Takeshi Ono
Hirotate Iwase
Somsak Mitrirattanakul
Kevin S. Omoto
Ting Cho
Yan Yan N. Lam
Bradley Snyder
Igor Spigelman
author_sort Yoshizo Matsuka
title Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
title_short Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
title_full Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
title_fullStr Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
title_full_unstemmed Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats
title_sort altered atp release and metabolism in dorsal root ganglia of neuropathic rats
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/18794
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