Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart
1 Department of Physiology, University of the Witwatersrand, Johannesburg, South Africa; and Departments of 2 Medicine and 3 Physiology, University of Massachusetts, Worcester, Massachusetts 01655 Presently, the physiological significance of myocardial adenosine A 2a receptor stimulation is uncle...
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| Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 1999-02, Vol.276 (2), p.H341 |
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| creator | Norton, Gavin R Woodiwiss, Angela J McGinn, Robert J Lorbar, Mojca Chung, Eugene S Honeyman, Thomas W Fenton, Richard A Dobson, James G., Jr Meyer, Theo E |
| description | 1 Department of Physiology,
University of the Witwatersrand, Johannesburg, South Africa; and
Departments of 2 Medicine and
3 Physiology, University of
Massachusetts, Worcester, Massachusetts 01655
Presently, the physiological significance of
myocardial adenosine A 2a receptor
stimulation is unclear. In this study, the influence of adenosine
A 2a receptor activation on
A 1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat
hearts and isolated rat ventricular myocytes. In isolated perfused
hearts, the selective A 2a receptor
antagonists 8-(3-chlorostyryl)caffeine (CSC) and
4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10 8 M)-elicited
contractile responses (+dP/d t max ) in a
dose-dependent manner. The effect of ZM-241385 on adenosine-induced
antiadrenergic actions was abolished by the selective
A 1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
(10 7 M), but not the
selective A 3 receptor antagonist
3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10 7 M). The
A 2a receptor agonist
carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at
10 5 M attenuated the
antiadrenergic effect of the selective
A 1 receptor agonist
2-chloro- N 6 -cyclopentyladenosine
(CCPA), whereas CSC did not influence the antiadrenergic action of this
agonist. In isolated ventricular myocytes, CSC potentiated the
inhibitory action of adenosine on Iso (2 × 10 7 M)-elicited increases
in intracellular Ca 2+
concentration
([Ca 2+ ] i )
transients but did not influence Iso-induced changes in
[Ca 2+ ] i
transients in the absence of exogenous adenosine. These results indicate that adenosine A 2a
receptor antagonists enhance
A 1 -receptor-induced antiadrenergic
responses and that A 2a receptor
agonists attenuate (albeit to a modest degree) the antiadrenergic
actions of A 1 receptor activation.
In conclusion, the data in this study support the notion that an
important physiological role of
A 2a receptors in the normal
mammalian myocardium is to reduce
A 1 receptor-mediated antiadrenergic actions.
A 3 receptor; perfused hearts; ventricular myocytes; isoproterenol; calcium |
| doi_str_mv | 10.1152/ajpheart.1999.276.2.H341 |
| format | Article |
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University of the Witwatersrand, Johannesburg, South Africa; and
Departments of 2 Medicine and
3 Physiology, University of
Massachusetts, Worcester, Massachusetts 01655
Presently, the physiological significance of
myocardial adenosine A 2a receptor
stimulation is unclear. In this study, the influence of adenosine
A 2a receptor activation on
A 1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat
hearts and isolated rat ventricular myocytes. In isolated perfused
hearts, the selective A 2a receptor
antagonists 8-(3-chlorostyryl)caffeine (CSC) and
4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10 8 M)-elicited
contractile responses (+dP/d t max ) in a
dose-dependent manner. The effect of ZM-241385 on adenosine-induced
antiadrenergic actions was abolished by the selective
A 1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
(10 7 M), but not the
selective A 3 receptor antagonist
3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10 7 M). The
A 2a receptor agonist
carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at
10 5 M attenuated the
antiadrenergic effect of the selective
A 1 receptor agonist
2-chloro- N 6 -cyclopentyladenosine
(CCPA), whereas CSC did not influence the antiadrenergic action of this
agonist. In isolated ventricular myocytes, CSC potentiated the
inhibitory action of adenosine on Iso (2 × 10 7 M)-elicited increases
in intracellular Ca 2+
concentration
([Ca 2+ ] i )
transients but did not influence Iso-induced changes in
[Ca 2+ ] i
transients in the absence of exogenous adenosine. These results indicate that adenosine A 2a
receptor antagonists enhance
A 1 -receptor-induced antiadrenergic
responses and that A 2a receptor
agonists attenuate (albeit to a modest degree) the antiadrenergic
actions of A 1 receptor activation.
In conclusion, the data in this study support the notion that an
important physiological role of
A 2a receptors in the normal
mammalian myocardium is to reduce
A 1 receptor-mediated antiadrenergic actions.
A 3 receptor; perfused hearts; ventricular myocytes; isoproterenol; calcium</description><identifier>ISSN: 0363-6135</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.1999.276.2.H341</identifier><identifier>PMID: 9950832</identifier><language>eng</language><publisher>United States</publisher><subject>Adenosine - pharmacology ; Adrenergic alpha-Antagonists - pharmacology ; Animals ; Calcium - metabolism ; Drug Synergism ; Heart - drug effects ; In Vitro Techniques ; Intracellular Membranes - metabolism ; Male ; Myocardium - cytology ; Myocardium - metabolism ; Osmolar Concentration ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P1 - physiology ; Triazines - antagonists & inhibitors ; Triazines - pharmacology ; Triazoles - antagonists & inhibitors ; Triazoles - pharmacology</subject><ispartof>American journal of physiology. Heart and circulatory physiology, 1999-02, Vol.276 (2), p.H341</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9950832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Norton, Gavin R</creatorcontrib><creatorcontrib>Woodiwiss, Angela J</creatorcontrib><creatorcontrib>McGinn, Robert J</creatorcontrib><creatorcontrib>Lorbar, Mojca</creatorcontrib><creatorcontrib>Chung, Eugene S</creatorcontrib><creatorcontrib>Honeyman, Thomas W</creatorcontrib><creatorcontrib>Fenton, Richard A</creatorcontrib><creatorcontrib>Dobson, James G., Jr</creatorcontrib><creatorcontrib>Meyer, Theo E</creatorcontrib><title>Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol</addtitle><description>1 Department of Physiology,
University of the Witwatersrand, Johannesburg, South Africa; and
Departments of 2 Medicine and
3 Physiology, University of
Massachusetts, Worcester, Massachusetts 01655
Presently, the physiological significance of
myocardial adenosine A 2a receptor
stimulation is unclear. In this study, the influence of adenosine
A 2a receptor activation on
A 1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat
hearts and isolated rat ventricular myocytes. In isolated perfused
hearts, the selective A 2a receptor
antagonists 8-(3-chlorostyryl)caffeine (CSC) and
4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10 8 M)-elicited
contractile responses (+dP/d t max ) in a
dose-dependent manner. The effect of ZM-241385 on adenosine-induced
antiadrenergic actions was abolished by the selective
A 1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
(10 7 M), but not the
selective A 3 receptor antagonist
3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10 7 M). The
A 2a receptor agonist
carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at
10 5 M attenuated the
antiadrenergic effect of the selective
A 1 receptor agonist
2-chloro- N 6 -cyclopentyladenosine
(CCPA), whereas CSC did not influence the antiadrenergic action of this
agonist. In isolated ventricular myocytes, CSC potentiated the
inhibitory action of adenosine on Iso (2 × 10 7 M)-elicited increases
in intracellular Ca 2+
concentration
([Ca 2+ ] i )
transients but did not influence Iso-induced changes in
[Ca 2+ ] i
transients in the absence of exogenous adenosine. These results indicate that adenosine A 2a
receptor antagonists enhance
A 1 -receptor-induced antiadrenergic
responses and that A 2a receptor
agonists attenuate (albeit to a modest degree) the antiadrenergic
actions of A 1 receptor activation.
In conclusion, the data in this study support the notion that an
important physiological role of
A 2a receptors in the normal
mammalian myocardium is to reduce
A 1 receptor-mediated antiadrenergic actions.
A 3 receptor; perfused hearts; ventricular myocytes; isoproterenol; calcium</description><subject>Adenosine - pharmacology</subject><subject>Adrenergic alpha-Antagonists - pharmacology</subject><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Drug Synergism</subject><subject>Heart - drug effects</subject><subject>In Vitro Techniques</subject><subject>Intracellular Membranes - metabolism</subject><subject>Male</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Osmolar Concentration</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Purinergic P1 - physiology</subject><subject>Triazines - antagonists & inhibitors</subject><subject>Triazines - pharmacology</subject><subject>Triazoles - antagonists & inhibitors</subject><subject>Triazoles - pharmacology</subject><issn>0363-6135</issn><issn>0002-9513</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOwzAQRS0EKqXwCUj-gQS_ksbsKsRLQmJT1tbEnjQuaRI5LtC_J7Q8VqxGmnvPaO4lhHKWcp6JK1j3NUKIKddap2KepyJ9kIofkekoi4RnUh-TKZO5THIus1NyNgxrxlg2z-WETLTOWCHFlLwuHLbd4FukC04DWuxjF5INOg8RHYU2enABWwwrbylWFdo4UAhIN53bNntTuaMLAb80BRv9G0TftdS3NECk-2fPyUkFzYAX33NGXu5ulzcPydPz_ePN4impuZIicbpiimUFoFDjwroCSmXBOm6FQqnUXKsiz5SsZFnIsiwKl9lSAM4t0xpKOSOXh7v9thyDmD74DYSd-Q496tcHvfar-t0HNH29G3zXdKududs2zRI_ovmpeCzXCPNVruldNcLp__APY_4g-QksfoOK</recordid><startdate>19990201</startdate><enddate>19990201</enddate><creator>Norton, Gavin R</creator><creator>Woodiwiss, Angela J</creator><creator>McGinn, Robert J</creator><creator>Lorbar, Mojca</creator><creator>Chung, Eugene S</creator><creator>Honeyman, Thomas W</creator><creator>Fenton, Richard A</creator><creator>Dobson, James G., Jr</creator><creator>Meyer, Theo E</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19990201</creationdate><title>Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart</title><author>Norton, Gavin R ; Woodiwiss, Angela J ; McGinn, Robert J ; Lorbar, Mojca ; Chung, Eugene S ; Honeyman, Thomas W ; Fenton, Richard A ; Dobson, James G., Jr ; Meyer, Theo E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h1432-d9f04058ae24143cd8ab4cacd1c24e34479486543f3b83bb88d5cb2ae7c099ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenosine - pharmacology</topic><topic>Adrenergic alpha-Antagonists - pharmacology</topic><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Drug Synergism</topic><topic>Heart - drug effects</topic><topic>In Vitro Techniques</topic><topic>Intracellular Membranes - metabolism</topic><topic>Male</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Osmolar Concentration</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Purinergic P1 - physiology</topic><topic>Triazines - antagonists & inhibitors</topic><topic>Triazines - pharmacology</topic><topic>Triazoles - antagonists & inhibitors</topic><topic>Triazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Norton, Gavin R</creatorcontrib><creatorcontrib>Woodiwiss, Angela J</creatorcontrib><creatorcontrib>McGinn, Robert J</creatorcontrib><creatorcontrib>Lorbar, Mojca</creatorcontrib><creatorcontrib>Chung, Eugene S</creatorcontrib><creatorcontrib>Honeyman, Thomas W</creatorcontrib><creatorcontrib>Fenton, Richard A</creatorcontrib><creatorcontrib>Dobson, James G., Jr</creatorcontrib><creatorcontrib>Meyer, Theo E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Norton, Gavin R</au><au>Woodiwiss, Angela J</au><au>McGinn, Robert J</au><au>Lorbar, Mojca</au><au>Chung, Eugene S</au><au>Honeyman, Thomas W</au><au>Fenton, Richard A</au><au>Dobson, James G., Jr</au><au>Meyer, Theo E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol</addtitle><date>1999-02-01</date><risdate>1999</risdate><volume>276</volume><issue>2</issue><spage>H341</spage><pages>H341-</pages><issn>0363-6135</issn><issn>0002-9513</issn><eissn>1522-1539</eissn><abstract>1 Department of Physiology,
University of the Witwatersrand, Johannesburg, South Africa; and
Departments of 2 Medicine and
3 Physiology, University of
Massachusetts, Worcester, Massachusetts 01655
Presently, the physiological significance of
myocardial adenosine A 2a receptor
stimulation is unclear. In this study, the influence of adenosine
A 2a receptor activation on
A 1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat
hearts and isolated rat ventricular myocytes. In isolated perfused
hearts, the selective A 2a receptor
antagonists 8-(3-chlorostyryl)caffeine (CSC) and
4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10 8 M)-elicited
contractile responses (+dP/d t max ) in a
dose-dependent manner. The effect of ZM-241385 on adenosine-induced
antiadrenergic actions was abolished by the selective
A 1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
(10 7 M), but not the
selective A 3 receptor antagonist
3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10 7 M). The
A 2a receptor agonist
carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at
10 5 M attenuated the
antiadrenergic effect of the selective
A 1 receptor agonist
2-chloro- N 6 -cyclopentyladenosine
(CCPA), whereas CSC did not influence the antiadrenergic action of this
agonist. In isolated ventricular myocytes, CSC potentiated the
inhibitory action of adenosine on Iso (2 × 10 7 M)-elicited increases
in intracellular Ca 2+
concentration
([Ca 2+ ] i )
transients but did not influence Iso-induced changes in
[Ca 2+ ] i
transients in the absence of exogenous adenosine. These results indicate that adenosine A 2a
receptor antagonists enhance
A 1 -receptor-induced antiadrenergic
responses and that A 2a receptor
agonists attenuate (albeit to a modest degree) the antiadrenergic
actions of A 1 receptor activation.
In conclusion, the data in this study support the notion that an
important physiological role of
A 2a receptors in the normal
mammalian myocardium is to reduce
A 1 receptor-mediated antiadrenergic actions.
A 3 receptor; perfused hearts; ventricular myocytes; isoproterenol; calcium</abstract><cop>United States</cop><pmid>9950832</pmid><doi>10.1152/ajpheart.1999.276.2.H341</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0363-6135 |
| ispartof | American journal of physiology. Heart and circulatory physiology, 1999-02, Vol.276 (2), p.H341 |
| issn | 0363-6135 0002-9513 1522-1539 |
| language | eng |
| recordid | cdi_highwire_physiology_ajpheart_276_2_H341 |
| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adenosine - pharmacology Adrenergic alpha-Antagonists - pharmacology Animals Calcium - metabolism Drug Synergism Heart - drug effects In Vitro Techniques Intracellular Membranes - metabolism Male Myocardium - cytology Myocardium - metabolism Osmolar Concentration Rats Rats, Sprague-Dawley Receptors, Purinergic P1 - physiology Triazines - antagonists & inhibitors Triazines - pharmacology Triazoles - antagonists & inhibitors Triazoles - pharmacology |
| title | Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart |
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