Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release
Departments of Pharmacological and Physiological Science and Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri 63104 Previously, we reported that red blood cells (RBCs) of rabbits and humans release ATP in response to mechanical deformation and that this release of AT...
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creator | Sprague, Randy S Ellsworth, Mary L Stephenson, Alan H Lonigro, Andrew J |
description | Departments of Pharmacological and Physiological Science and
Internal Medicine, Saint Louis University School of Medicine, St.
Louis, Missouri 63104
Previously, we reported
that red blood cells (RBCs) of rabbits and humans release ATP in
response to mechanical deformation and that this release of ATP
requires the activity of the cystic fibrosis transmembrane conductance
regulator (CFTR). It was reported that cAMP, acting through a
cAMP-dependent protein kinase, PKA, is an activator of CFTR. Here we
investigate the hypothesis that cAMP stimulates ATP release from RBCs.
Incubation of human and rabbit RBCs with the direct activator of
adenylyl cyclase, forskolin (10 or 100 µM), with IBMX (100 µM),
resulted in ATP release and increases in intracellular cAMP. In
addition, epinephrine (1 µM), a receptor-mediated activator of
adenylyl cyclase, stimulated ATP release from rabbit RBCs. Moreover,
incubation of human and rabbit RBCs with an active cAMP analog
[adenosine 3'5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP, 100 µM)] resulted in ATP release. In contrast, forskolin and Sp-cAMP
were without effect on dog RBCs, cells known not to release ATP in
response to deformation. When rabbit RBCs were incubated with the
inactive cAMP analog and inhibitor of PKA activity, adenosine
3',5'-cyclic monophosphorothioate Rp-isomer (100 µM),
deformation-induced ATP release was attenuated. These results are
consistent with the hypothesis that adenylyl cyclase and cAMP are
components of a signal-transduction pathway relating RBC deformation to
ATP release from human and rabbit RBCs.
pulmonary circulation; red blood cells; cystic fibrosis
transmembrane conductance regulator; nitric oxide |
doi_str_mv | 10.1152/ajpcell.2001.281.4.c1158 |
format | Article |
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Internal Medicine, Saint Louis University School of Medicine, St.
Louis, Missouri 63104
Previously, we reported
that red blood cells (RBCs) of rabbits and humans release ATP in
response to mechanical deformation and that this release of ATP
requires the activity of the cystic fibrosis transmembrane conductance
regulator (CFTR). It was reported that cAMP, acting through a
cAMP-dependent protein kinase, PKA, is an activator of CFTR. Here we
investigate the hypothesis that cAMP stimulates ATP release from RBCs.
Incubation of human and rabbit RBCs with the direct activator of
adenylyl cyclase, forskolin (10 or 100 µM), with IBMX (100 µM),
resulted in ATP release and increases in intracellular cAMP. In
addition, epinephrine (1 µM), a receptor-mediated activator of
adenylyl cyclase, stimulated ATP release from rabbit RBCs. Moreover,
incubation of human and rabbit RBCs with an active cAMP analog
[adenosine 3'5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP, 100 µM)] resulted in ATP release. In contrast, forskolin and Sp-cAMP
were without effect on dog RBCs, cells known not to release ATP in
response to deformation. When rabbit RBCs were incubated with the
inactive cAMP analog and inhibitor of PKA activity, adenosine
3',5'-cyclic monophosphorothioate Rp-isomer (100 µM),
deformation-induced ATP release was attenuated. These results are
consistent with the hypothesis that adenylyl cyclase and cAMP are
components of a signal-transduction pathway relating RBC deformation to
ATP release from human and rabbit RBCs.
pulmonary circulation; red blood cells; cystic fibrosis
transmembrane conductance regulator; nitric oxide</description><identifier>ISSN: 0363-6143</identifier><identifier>EISSN: 1522-1563</identifier><identifier>DOI: 10.1152/ajpcell.2001.281.4.c1158</identifier><identifier>PMID: 11546651</identifier><language>eng</language><publisher>United States</publisher><subject>1-Methyl-3-isobutylxanthine - pharmacology ; Adenosine Triphosphate - metabolism ; Animals ; Colforsin - pharmacology ; Cyclic AMP - analogs & derivatives ; Cyclic AMP - metabolism ; Cyclic AMP - pharmacology ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism ; Dogs ; Enzyme Inhibitors - pharmacology ; Erythrocyte Deformability - physiology ; Humans ; Male ; Nitric Oxide - metabolism ; Phosphodiesterase Inhibitors - pharmacology ; Pulmonary Circulation - physiology ; Rabbits ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Space life sciences ; Thionucleotides - pharmacology</subject><ispartof>American Journal of Physiology: Cell Physiology, 2001-10, Vol.281 (4), p.C1158-C1164</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-cfe609dfef7900daf6d0218a765be28a8e7be1312cbb0b0b1b8090c748c69c063</citedby><cites>FETCH-LOGICAL-c522t-cfe609dfef7900daf6d0218a765be28a8e7be1312cbb0b0b1b8090c748c69c063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3026,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11546651$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sprague, Randy S</creatorcontrib><creatorcontrib>Ellsworth, Mary L</creatorcontrib><creatorcontrib>Stephenson, Alan H</creatorcontrib><creatorcontrib>Lonigro, Andrew J</creatorcontrib><title>Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release</title><title>American Journal of Physiology: Cell Physiology</title><addtitle>Am J Physiol Cell Physiol</addtitle><description>Departments of Pharmacological and Physiological Science and
Internal Medicine, Saint Louis University School of Medicine, St.
Louis, Missouri 63104
Previously, we reported
that red blood cells (RBCs) of rabbits and humans release ATP in
response to mechanical deformation and that this release of ATP
requires the activity of the cystic fibrosis transmembrane conductance
regulator (CFTR). It was reported that cAMP, acting through a
cAMP-dependent protein kinase, PKA, is an activator of CFTR. Here we
investigate the hypothesis that cAMP stimulates ATP release from RBCs.
Incubation of human and rabbit RBCs with the direct activator of
adenylyl cyclase, forskolin (10 or 100 µM), with IBMX (100 µM),
resulted in ATP release and increases in intracellular cAMP. In
addition, epinephrine (1 µM), a receptor-mediated activator of
adenylyl cyclase, stimulated ATP release from rabbit RBCs. Moreover,
incubation of human and rabbit RBCs with an active cAMP analog
[adenosine 3'5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP, 100 µM)] resulted in ATP release. In contrast, forskolin and Sp-cAMP
were without effect on dog RBCs, cells known not to release ATP in
response to deformation. When rabbit RBCs were incubated with the
inactive cAMP analog and inhibitor of PKA activity, adenosine
3',5'-cyclic monophosphorothioate Rp-isomer (100 µM),
deformation-induced ATP release was attenuated. These results are
consistent with the hypothesis that adenylyl cyclase and cAMP are
components of a signal-transduction pathway relating RBC deformation to
ATP release from human and rabbit RBCs.
pulmonary circulation; red blood cells; cystic fibrosis
transmembrane conductance regulator; nitric oxide</description><subject>1-Methyl-3-isobutylxanthine - pharmacology</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Animals</subject><subject>Colforsin - pharmacology</subject><subject>Cyclic AMP - analogs & derivatives</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP - pharmacology</subject><subject>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</subject><subject>Dogs</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Erythrocyte Deformability - physiology</subject><subject>Humans</subject><subject>Male</subject><subject>Nitric Oxide - metabolism</subject><subject>Phosphodiesterase Inhibitors - pharmacology</subject><subject>Pulmonary Circulation - physiology</subject><subject>Rabbits</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Space life sciences</subject><subject>Thionucleotides - pharmacology</subject><issn>0363-6143</issn><issn>1522-1563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFu3CAURVHUqpkm_YWIVXd2AXsw7m40apJKiTqLyRph_BgTeYwLWKn_vrgzVZpF9RYs3rn3oYMQpiSndM2-qOdRQ9_njBCaM0HzMtdpIS7QKq1ZRte8eIdWpOBFxmlZXKKPITwTQkrG6w_oMrEl52u6QmanfLTajipaN2BnsN487rAdsMLBHgbVZ9GrIbST_gMkrntRM_bQp8RwwODn2Hmn5wi4BeP88dQUHd7sdwsHKsA1em9UH-DT-b1CT7ff9tv77OHH3fft5iHT6dsx0wY4qVsDpqoJaZXhLWFUqIqvG2BCCagaoAVlumlIGtoIUhNdlULzWhNeXKHPp97Ru58ThCiPNiyq1ABuCrKiVDBRiwSKE6i9C8GDkaO3R-VnSYlcHMuzY7k4lsmxLOV2cZyiN-cbU3OE9jV4lpqA_AR09tC9WA9y7OZgXe8O82vtm8av_w_cTn2_h1_xb_KfoBxbU_wGzG2hrQ</recordid><startdate>20011001</startdate><enddate>20011001</enddate><creator>Sprague, Randy S</creator><creator>Ellsworth, Mary L</creator><creator>Stephenson, Alan H</creator><creator>Lonigro, Andrew J</creator><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>7X8</scope></search><sort><creationdate>20011001</creationdate><title>Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release</title><author>Sprague, Randy S ; Ellsworth, Mary L ; Stephenson, Alan H ; Lonigro, Andrew J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-cfe609dfef7900daf6d0218a765be28a8e7be1312cbb0b0b1b8090c748c69c063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>1-Methyl-3-isobutylxanthine - pharmacology</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Animals</topic><topic>Colforsin - pharmacology</topic><topic>Cyclic AMP - analogs & derivatives</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP - pharmacology</topic><topic>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</topic><topic>Dogs</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Erythrocyte Deformability - physiology</topic><topic>Humans</topic><topic>Male</topic><topic>Nitric Oxide - metabolism</topic><topic>Phosphodiesterase Inhibitors - pharmacology</topic><topic>Pulmonary Circulation - physiology</topic><topic>Rabbits</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Space life sciences</topic><topic>Thionucleotides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sprague, Randy S</creatorcontrib><creatorcontrib>Ellsworth, Mary L</creatorcontrib><creatorcontrib>Stephenson, Alan H</creatorcontrib><creatorcontrib>Lonigro, Andrew J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sprague, Randy S</au><au>Ellsworth, Mary L</au><au>Stephenson, Alan H</au><au>Lonigro, Andrew J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>281</volume><issue>4</issue><spage>C1158</spage><epage>C1164</epage><pages>C1158-C1164</pages><issn>0363-6143</issn><eissn>1522-1563</eissn><abstract>Departments of Pharmacological and Physiological Science and
Internal Medicine, Saint Louis University School of Medicine, St.
Louis, Missouri 63104
Previously, we reported
that red blood cells (RBCs) of rabbits and humans release ATP in
response to mechanical deformation and that this release of ATP
requires the activity of the cystic fibrosis transmembrane conductance
regulator (CFTR). It was reported that cAMP, acting through a
cAMP-dependent protein kinase, PKA, is an activator of CFTR. Here we
investigate the hypothesis that cAMP stimulates ATP release from RBCs.
Incubation of human and rabbit RBCs with the direct activator of
adenylyl cyclase, forskolin (10 or 100 µM), with IBMX (100 µM),
resulted in ATP release and increases in intracellular cAMP. In
addition, epinephrine (1 µM), a receptor-mediated activator of
adenylyl cyclase, stimulated ATP release from rabbit RBCs. Moreover,
incubation of human and rabbit RBCs with an active cAMP analog
[adenosine 3'5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP, 100 µM)] resulted in ATP release. In contrast, forskolin and Sp-cAMP
were without effect on dog RBCs, cells known not to release ATP in
response to deformation. When rabbit RBCs were incubated with the
inactive cAMP analog and inhibitor of PKA activity, adenosine
3',5'-cyclic monophosphorothioate Rp-isomer (100 µM),
deformation-induced ATP release was attenuated. These results are
consistent with the hypothesis that adenylyl cyclase and cAMP are
components of a signal-transduction pathway relating RBC deformation to
ATP release from human and rabbit RBCs.
pulmonary circulation; red blood cells; cystic fibrosis
transmembrane conductance regulator; nitric oxide</abstract><cop>United States</cop><pmid>11546651</pmid><doi>10.1152/ajpcell.2001.281.4.c1158</doi></addata></record> |
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source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
subjects | 1-Methyl-3-isobutylxanthine - pharmacology Adenosine Triphosphate - metabolism Animals Colforsin - pharmacology Cyclic AMP - analogs & derivatives Cyclic AMP - metabolism Cyclic AMP - pharmacology Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - metabolism Cystic Fibrosis Transmembrane Conductance Regulator - metabolism Dogs Enzyme Inhibitors - pharmacology Erythrocyte Deformability - physiology Humans Male Nitric Oxide - metabolism Phosphodiesterase Inhibitors - pharmacology Pulmonary Circulation - physiology Rabbits Signal Transduction - drug effects Signal Transduction - physiology Space life sciences Thionucleotides - pharmacology |
title | Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release |
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