Loading…
ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP
In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracell...
Saved in:
| Published in: | PloS one 2013-06, Vol.8 (6), p.e67117-e67117 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03 |
| container_end_page | e67117 |
| container_issue | 6 |
| container_start_page | e67117 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Burzaco, Jaione Conde, Manuel Parada, Luis A Zugaza, José L Dehaye, Jean-Paul Marino, Aida |
| description | In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca(2+)]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ-22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists. |
| doi_str_mv | 10.1371/journal.pone.0067117 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1370901042</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_b3727217a0ad485dac282289d9faba5e</doaj_id><sourcerecordid>3003896961</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03</originalsourceid><addsrcrecordid>eNptUtFu0zAUtRCIjY4_QBCJl_GQ7tpOYudlUjUVNmmISuueLcd2UlepXewECb4ed82mDfFk6_icc-89vgh9wDDHlOGLrR-Dk_18752ZA1QMY_YKneKakrwiQF8_u5-gdzFuAUrKq-otOiGUk4SzU7RarFeZdIPsvLN_TMyGTfC7xrrcOj0qo7Nou1QmG4J0MSGD9e6BNHabDJPzuy_59XK9TB46U4vvqzP0ppV9NO-nc4buvy7XV9f57Y9vN1eL21yVpBpyxcuqIRxj1RJdaN7W0AA0mkmuZQG6rEmaiGoG2NDUuAKiqNSYkaQEA3SGPh19972PYgojihQN1IChIIlxc2RoL7diH-xOht_CSyseAB86IcNgVW9EQxlhBDMJUhe81FIRTgivdd3KRpYmeV1O1cZmZ7QyLuXRvzB9-eLsRnT-l6BVjTGpk8H5ZBD8z9HEQexsVKbvpTN-PPRd84IWLH3RDH3-h_r_6YojSwUfYzDtUzMYDjz8qBKHBRHTgiTZx-eDPIkeN4L-BedOt00</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1370901042</pqid></control><display><type>article</type><title>ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP</title><source>PubMed Central Free</source><source>Publicly Available Content Database</source><creator>Burzaco, Jaione ; Conde, Manuel ; Parada, Luis A ; Zugaza, José L ; Dehaye, Jean-Paul ; Marino, Aida</creator><contributor>Roberts, David D.</contributor><creatorcontrib>Burzaco, Jaione ; Conde, Manuel ; Parada, Luis A ; Zugaza, José L ; Dehaye, Jean-Paul ; Marino, Aida ; Roberts, David D.</creatorcontrib><description>In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca(2+)]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ-22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067117</identifier><identifier>PMID: 23826207</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism ; Acids ; Adenosine ; Adenosine deaminase ; Adenosine Deaminase - metabolism ; Adenosine Triphosphate - pharmacology ; Adenylate cyclase ; Agglomeration ; Apyrase ; Apyrase - metabolism ; Arachidonate 12-lipoxygenase ; Arachidonate 12-Lipoxygenase - metabolism ; ATP ; Binding sites ; Biochemistry ; Biology ; Blood platelets ; Calcium (intracellular) ; Calcium Signaling - drug effects ; Cyclic AMP ; Cyclic AMP - metabolism ; Human behavior ; Humans ; Hypertension ; Inhibition ; Inositol 1,4,5-trisphosphate ; Inositol phosphates ; Inositol trisphosphate ; Kinases ; Laboratories ; Lipoxygenase ; Magnesium ; Magnesium - pharmacology ; Medicine ; Molecular biology ; Phosphates ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - pharmacology ; Platelets ; Pretreatment ; Proteins ; Purinergic P2Y Receptor Antagonists - pharmacology ; Receptors ; Receptors, Purinergic P2Y1 - metabolism ; Receptors, Purinergic P2Y12 - metabolism ; Science ; Signal transduction ; Signal Transduction - drug effects ; Thrombin ; Thrombin - pharmacology ; Thrombosis ; Time Factors ; Transduction</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e67117-e67117</ispartof><rights>2013 Burzaco et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Burzaco et al 2013 Burzaco et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03</citedby><cites>FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1370901042/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1370901042?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23826207$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Roberts, David D.</contributor><creatorcontrib>Burzaco, Jaione</creatorcontrib><creatorcontrib>Conde, Manuel</creatorcontrib><creatorcontrib>Parada, Luis A</creatorcontrib><creatorcontrib>Zugaza, José L</creatorcontrib><creatorcontrib>Dehaye, Jean-Paul</creatorcontrib><creatorcontrib>Marino, Aida</creatorcontrib><title>ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca(2+)]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ-22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.</description><subject>12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism</subject><subject>Acids</subject><subject>Adenosine</subject><subject>Adenosine deaminase</subject><subject>Adenosine Deaminase - metabolism</subject><subject>Adenosine Triphosphate - pharmacology</subject><subject>Adenylate cyclase</subject><subject>Agglomeration</subject><subject>Apyrase</subject><subject>Apyrase - metabolism</subject><subject>Arachidonate 12-lipoxygenase</subject><subject>Arachidonate 12-Lipoxygenase - metabolism</subject><subject>ATP</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Blood platelets</subject><subject>Calcium (intracellular)</subject><subject>Calcium Signaling - drug effects</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - metabolism</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Inhibition</subject><subject>Inositol 1,4,5-trisphosphate</subject><subject>Inositol phosphates</subject><subject>Inositol trisphosphate</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lipoxygenase</subject><subject>Magnesium</subject><subject>Magnesium - pharmacology</subject><subject>Medicine</subject><subject>Molecular biology</subject><subject>Phosphates</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Platelets</subject><subject>Pretreatment</subject><subject>Proteins</subject><subject>Purinergic P2Y Receptor Antagonists - pharmacology</subject><subject>Receptors</subject><subject>Receptors, Purinergic P2Y1 - metabolism</subject><subject>Receptors, Purinergic P2Y12 - metabolism</subject><subject>Science</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Thrombin</subject><subject>Thrombin - pharmacology</subject><subject>Thrombosis</subject><subject>Time Factors</subject><subject>Transduction</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUtFu0zAUtRCIjY4_QBCJl_GQ7tpOYudlUjUVNmmISuueLcd2UlepXewECb4ed82mDfFk6_icc-89vgh9wDDHlOGLrR-Dk_18752ZA1QMY_YKneKakrwiQF8_u5-gdzFuAUrKq-otOiGUk4SzU7RarFeZdIPsvLN_TMyGTfC7xrrcOj0qo7Nou1QmG4J0MSGD9e6BNHabDJPzuy_59XK9TB46U4vvqzP0ppV9NO-nc4buvy7XV9f57Y9vN1eL21yVpBpyxcuqIRxj1RJdaN7W0AA0mkmuZQG6rEmaiGoG2NDUuAKiqNSYkaQEA3SGPh19972PYgojihQN1IChIIlxc2RoL7diH-xOht_CSyseAB86IcNgVW9EQxlhBDMJUhe81FIRTgivdd3KRpYmeV1O1cZmZ7QyLuXRvzB9-eLsRnT-l6BVjTGpk8H5ZBD8z9HEQexsVKbvpTN-PPRd84IWLH3RDH3-h_r_6YojSwUfYzDtUzMYDjz8qBKHBRHTgiTZx-eDPIkeN4L-BedOt00</recordid><startdate>20130624</startdate><enddate>20130624</enddate><creator>Burzaco, Jaione</creator><creator>Conde, Manuel</creator><creator>Parada, Luis A</creator><creator>Zugaza, José L</creator><creator>Dehaye, Jean-Paul</creator><creator>Marino, Aida</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130624</creationdate><title>ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP</title><author>Burzaco, Jaione ; Conde, Manuel ; Parada, Luis A ; Zugaza, José L ; Dehaye, Jean-Paul ; Marino, Aida</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism</topic><topic>Acids</topic><topic>Adenosine</topic><topic>Adenosine deaminase</topic><topic>Adenosine Deaminase - metabolism</topic><topic>Adenosine Triphosphate - pharmacology</topic><topic>Adenylate cyclase</topic><topic>Agglomeration</topic><topic>Apyrase</topic><topic>Apyrase - metabolism</topic><topic>Arachidonate 12-lipoxygenase</topic><topic>Arachidonate 12-Lipoxygenase - metabolism</topic><topic>ATP</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Blood platelets</topic><topic>Calcium (intracellular)</topic><topic>Calcium Signaling - drug effects</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - metabolism</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Inhibition</topic><topic>Inositol 1,4,5-trisphosphate</topic><topic>Inositol phosphates</topic><topic>Inositol trisphosphate</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Lipoxygenase</topic><topic>Magnesium</topic><topic>Magnesium - pharmacology</topic><topic>Medicine</topic><topic>Molecular biology</topic><topic>Phosphates</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Platelets</topic><topic>Pretreatment</topic><topic>Proteins</topic><topic>Purinergic P2Y Receptor Antagonists - pharmacology</topic><topic>Receptors</topic><topic>Receptors, Purinergic P2Y1 - metabolism</topic><topic>Receptors, Purinergic P2Y12 - metabolism</topic><topic>Science</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Thrombin</topic><topic>Thrombin - pharmacology</topic><topic>Thrombosis</topic><topic>Time Factors</topic><topic>Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burzaco, Jaione</creatorcontrib><creatorcontrib>Conde, Manuel</creatorcontrib><creatorcontrib>Parada, Luis A</creatorcontrib><creatorcontrib>Zugaza, José L</creatorcontrib><creatorcontrib>Dehaye, Jean-Paul</creatorcontrib><creatorcontrib>Marino, Aida</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burzaco, Jaione</au><au>Conde, Manuel</au><au>Parada, Luis A</au><au>Zugaza, José L</au><au>Dehaye, Jean-Paul</au><au>Marino, Aida</au><au>Roberts, David D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-24</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e67117</spage><epage>e67117</epage><pages>e67117-e67117</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In this study we have investigated the role of extracellular ATP on thrombin induced-platelet aggregation (TIPA) in washed human platelets. ATP inhibited TIPA in a dose-dependent manner and this inhibition was abolished by apyrase but not by adenosine deaminase (ADA) and it was reversed by extracellular magnesium. Antagonists of P2Y1 and P2Y12 receptors had no effect on this inhibition suggesting that a P2X receptor controlled ATP-mediated TIPA inhibition. ATP also blocked inositol phosphates (IP1, IP2, IP3) generation and [Ca(2+)]i mobilization induced by thrombin. Thrombin reduced cAMP levels which were restored in the presence of ATP. SQ-22536, an adenylate cyclase (AC) inhibitor, partially reduced the inhibition exerted by ATP on TIPA. 12-lipoxygenase (12-LO) inhibitors, nordihidroguaretic acid (NDGA) and 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(S)-HETE), strongly prevented ATP-mediated TIPA inhibition. Additionally, ATP inhibited the increase of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) induced by thrombin. Pretreatment with both SQ-22536 and NDGA almost completely abolished ATP-mediated TIPA inhibition. Our results describe for the first time that ATP implicates both AC and 12-LO pathways in the inhibition of human platelets aggregation in response to agonists.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23826207</pmid><doi>10.1371/journal.pone.0067117</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-06, Vol.8 (6), p.e67117-e67117 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1370901042 |
| source | PubMed Central Free; Publicly Available Content Database |
| subjects | 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism Acids Adenosine Adenosine deaminase Adenosine Deaminase - metabolism Adenosine Triphosphate - pharmacology Adenylate cyclase Agglomeration Apyrase Apyrase - metabolism Arachidonate 12-lipoxygenase Arachidonate 12-Lipoxygenase - metabolism ATP Binding sites Biochemistry Biology Blood platelets Calcium (intracellular) Calcium Signaling - drug effects Cyclic AMP Cyclic AMP - metabolism Human behavior Humans Hypertension Inhibition Inositol 1,4,5-trisphosphate Inositol phosphates Inositol trisphosphate Kinases Laboratories Lipoxygenase Magnesium Magnesium - pharmacology Medicine Molecular biology Phosphates Platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - pharmacology Platelets Pretreatment Proteins Purinergic P2Y Receptor Antagonists - pharmacology Receptors Receptors, Purinergic P2Y1 - metabolism Receptors, Purinergic P2Y12 - metabolism Science Signal transduction Signal Transduction - drug effects Thrombin Thrombin - pharmacology Thrombosis Time Factors Transduction |
| title | ATP antagonizes thrombin-induced signal transduction through 12(S)-HETE and cAMP |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T04%3A56%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ATP%20antagonizes%20thrombin-induced%20signal%20transduction%20through%2012(S)-HETE%20and%20cAMP&rft.jtitle=PloS%20one&rft.au=Burzaco,%20Jaione&rft.date=2013-06-24&rft.volume=8&rft.issue=6&rft.spage=e67117&rft.epage=e67117&rft.pages=e67117-e67117&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0067117&rft_dat=%3Cproquest_plos_%3E3003896961%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c526t-c856b2811cf2d4d8f90b00bd7a8da40d5926713d701e3005c02c3ad172c850e03%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1370901042&rft_id=info:pmid/23826207&rfr_iscdi=true |