Subtypes of nucleoside transport inhibitory sites in heart: a quantitative autoradiographical analysis
Identifieur interne : 004A42 ( Main/Exploration ); précédent : 004A41; suivant : 004A43Subtypes of nucleoside transport inhibitory sites in heart: a quantitative autoradiographical analysis
Auteurs : Fiona E. Parkinson [Canada] ; Alexander S. Clanachan [Canada]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 1989.
English descriptors
- KwdEn :
- MESH :
- chemical , analogs & derivatives : Thioinosine.
- chemical , metabolism : Nucleosides.
- cytology : Myocardium.
- drug effects : Binding, Competitive.
- metabolism : Endothelium, Vascular, Myocardium.
- Animals, Autoradiography, Guinea Pigs, In Vitro Techniques, Male.
Abstract
We evaluated the interaction of several nucleoside transport inhibitors and substrates with the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR) to nucleoside transport sites in guinea pig cardiac sections. Using quantitative autoradiography, we determined inhibition constants for inhibition of [3H]NBMPR binding to both coronary endothelial cells and cardiac myocytes. We studied the interactions of NBMPR, nitrobenzylthioguanosine, dipyridamole, dilazep, hexobendine, lidoflazine, mioflazine, soluflazine, adenosine, inosine and uridine for these two cell types. Of the compounds tested in this study, lidoflazine (8.2 ×) and hexobendine (6.3 ×) have the greatest selectivity for coronary endothelial cell nucleoside transporters. All other compounds had 3-fold or less selectivity. Therefore, there is evidence of nucleoside transporter subtypes between endothelial cells and myocytes. This heterogeneity of transport inhibitory sites on nucleoside transporters may allow the development of agents to modulate selectively some of the cardiovascular effects of adenosine.
Url:
DOI: 10.1016/0014-2999(89)90396-8
Affiliations:
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Parkinson</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Pharmacology, 9-70 Medical Sciences Building, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Clanachan, Alexander S" sort="Clanachan, Alexander S" uniqKey="Clanachan A" first="Alexander S." last="Clanachan">Alexander S. Clanachan</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Pharmacology, 9-70 Medical Sciences Building, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Pharmacology</title><title level="j" type="abbrev">EJP</title><idno type="ISSN">0014-2999</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1989">1989</date><biblScope unit="volume">163</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="69">69</biblScope><biblScope unit="page" to="75">75</biblScope></imprint><idno type="ISSN">0014-2999</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-2999</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Autoradiography</term><term>Binding, Competitive (drug effects)</term><term>Endothelium, Vascular (metabolism)</term><term>Guinea Pigs</term><term>In Vitro Techniques</term><term>Male</term><term>Myocardium (cytology)</term><term>Myocardium (metabolism)</term><term>Nucleosides (metabolism)</term><term>Thioinosine (analogs & derivatives)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Thioinosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nucleosides</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Myocardium</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Binding, Competitive</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelium, Vascular</term><term>Myocardium</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Autoradiography</term><term>Guinea Pigs</term><term>In Vitro Techniques</term><term>Male</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We evaluated the interaction of several nucleoside transport inhibitors and substrates with the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR) to nucleoside transport sites in guinea pig cardiac sections. Using quantitative autoradiography, we determined inhibition constants for inhibition of [3H]NBMPR binding to both coronary endothelial cells and cardiac myocytes. We studied the interactions of NBMPR, nitrobenzylthioguanosine, dipyridamole, dilazep, hexobendine, lidoflazine, mioflazine, soluflazine, adenosine, inosine and uridine for these two cell types. Of the compounds tested in this study, lidoflazine (8.2 ×) and hexobendine (6.3 ×) have the greatest selectivity for coronary endothelial cell nucleoside transporters. All other compounds had 3-fold or less selectivity. Therefore, there is evidence of nucleoside transporter subtypes between endothelial cells and myocytes. This heterogeneity of transport inhibitory sites on nucleoside transporters may allow the development of agents to modulate selectively some of the cardiovascular effects of adenosine.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E." last="Parkinson">Fiona E. Parkinson</name></noRegion><name sortKey="Clanachan, Alexander S" sort="Clanachan, Alexander S" uniqKey="Clanachan A" first="Alexander S." last="Clanachan">Alexander S. Clanachan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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