Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries
Receptors for purines and pyrimidines are expressed throughout the cardiovascular system. This study investigated their functional expression in porcine isolated pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were prepared for isometric tension recording and preconstricted...
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Springer Verlag
2014
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| Online Access: | https://eprints.nottingham.ac.uk/34865/ http://link.springer.com/article/10.1007%2Fs11302-013-9403-2 |
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| author | Alsaqati, M. Chan, S.L.F. Ralevic, Vera |
| author_facet | Alsaqati, M. Chan, S.L.F. Ralevic, Vera |
| author_sort | Alsaqati, M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Receptors for purines and pyrimidines are expressed throughout the cardiovascular system. This study investigated their functional expression in porcine isolated pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were prepared for isometric tension recording and preconstricted with U46619, a thromboxane A2 mimetic; adenosine-5′-diphosphate (ADP), uridine-5′-triphosphate (UTP) and MRS2768, a selective P2Y2 agonist, were applied cumulatively, while adenosine-5′-triphosphate (ATP) and αβ-methylene-ATP (αβ-meATP) response curves were generated from single concentrations per tissue segment. Antagonists/enzyme inhibitors were applied prior to U46619 addition. ATP, αβ-meATP, UTP and MRS2768 induced vasoconstriction, with a potency order of αβ-meATP > MRS2768 > ATP ≥ UTP. Contractions to ATP and αβ-meATP were blocked by NF449, a selective P2X1 receptor antagonist. The contraction induced by ATP, but not UTP, was followed by vasorelaxation. Endothelium removal and DUP 697, a cyclooxygenase-2 inhibitor, had no significant effect on contraction to ATP but attenuated that to UTP, indicating actions at distinct receptors. MRS2578, a selective P2Y6 receptor antagonist, had no effect on contractions to UTP. ADP induced endothelium-dependent vasorelaxation which was inhibited by MRS2179, a selective P2Y1 receptor antagonist, or SCH58261, a selective adenosine A2A receptor antagonist. The contractions to ATP and αβ-meATP were attributed to actions at P2X1 receptors on the vascular smooth muscle, whereas it was shown for the first time that UTP induced an endothelium-dependent vasoconstriction which may involve P2Y2 and/or P2Y4 receptors. The relaxation induced by ADP is mediated by P2Y1 and A2A adenosine receptors. Porcine pancreatic arteries appear to lack vasorelaxant P2Y2 and P2Y4 receptors. |
| first_indexed | 2025-11-14T19:24:19Z |
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| id | nottingham-34865 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:24:19Z |
| publishDate | 2014 |
| publisher | Springer Verlag |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-348652020-05-04T16:47:16Z https://eprints.nottingham.ac.uk/34865/ Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries Alsaqati, M. Chan, S.L.F. Ralevic, Vera Receptors for purines and pyrimidines are expressed throughout the cardiovascular system. This study investigated their functional expression in porcine isolated pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were prepared for isometric tension recording and preconstricted with U46619, a thromboxane A2 mimetic; adenosine-5′-diphosphate (ADP), uridine-5′-triphosphate (UTP) and MRS2768, a selective P2Y2 agonist, were applied cumulatively, while adenosine-5′-triphosphate (ATP) and αβ-methylene-ATP (αβ-meATP) response curves were generated from single concentrations per tissue segment. Antagonists/enzyme inhibitors were applied prior to U46619 addition. ATP, αβ-meATP, UTP and MRS2768 induced vasoconstriction, with a potency order of αβ-meATP > MRS2768 > ATP ≥ UTP. Contractions to ATP and αβ-meATP were blocked by NF449, a selective P2X1 receptor antagonist. The contraction induced by ATP, but not UTP, was followed by vasorelaxation. Endothelium removal and DUP 697, a cyclooxygenase-2 inhibitor, had no significant effect on contraction to ATP but attenuated that to UTP, indicating actions at distinct receptors. MRS2578, a selective P2Y6 receptor antagonist, had no effect on contractions to UTP. ADP induced endothelium-dependent vasorelaxation which was inhibited by MRS2179, a selective P2Y1 receptor antagonist, or SCH58261, a selective adenosine A2A receptor antagonist. The contractions to ATP and αβ-meATP were attributed to actions at P2X1 receptors on the vascular smooth muscle, whereas it was shown for the first time that UTP induced an endothelium-dependent vasoconstriction which may involve P2Y2 and/or P2Y4 receptors. The relaxation induced by ADP is mediated by P2Y1 and A2A adenosine receptors. Porcine pancreatic arteries appear to lack vasorelaxant P2Y2 and P2Y4 receptors. Springer Verlag 2014-06-01 Article PeerReviewed Alsaqati, M., Chan, S.L.F. and Ralevic, Vera (2014) Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries. Purinergic Signalling, 10 (2). pp. 241-249. ISSN 1573-9546 αβ-meATP ATP UTP ADP MRS2578 P2Y1 P2Y2 P2X1 A2A adenosine receptors Vasoconstriction Vasorelaxation Endothelium doi:10.1007/s11302-013-9403-2 http://link.springer.com/article/10.1007%2Fs11302-013-9403-2 http://link.springer.com/article/10.1007%2Fs11302-013-9403-2 |
| spellingShingle | αβ-meATP ATP UTP ADP MRS2578 P2Y1 P2Y2 P2X1 A2A adenosine receptors Vasoconstriction Vasorelaxation Endothelium Alsaqati, M. Chan, S.L.F. Ralevic, Vera Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title | Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title_full | Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title_fullStr | Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title_full_unstemmed | Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title_short | Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| title_sort | investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries |
| topic | αβ-meATP ATP UTP ADP MRS2578 P2Y1 P2Y2 P2X1 A2A adenosine receptors Vasoconstriction Vasorelaxation Endothelium |
| url | https://eprints.nottingham.ac.uk/34865/ https://eprints.nottingham.ac.uk/34865/ https://eprints.nottingham.ac.uk/34865/ http://link.springer.com/article/10.1007%2Fs11302-013-9403-2 |