The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation
Beta-Adrenoceptors (B-ARs) mediate vasodilatation by activating various mechanisms that collectively contribute to vascular smooth muscle (VSM) relaxation. It has been shown that B2-AR stimulation in cultured cells results in activation of extracellular signal-regulated kinase (ERK). As the function...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2012
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| Online Access: | https://eprints.nottingham.ac.uk/12695/ |
| _version_ | 1848791561173729280 |
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| author | Uhiara, Chukwuemeka Obinna |
| author_facet | Uhiara, Chukwuemeka Obinna |
| author_sort | Uhiara, Chukwuemeka Obinna |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Beta-Adrenoceptors (B-ARs) mediate vasodilatation by activating various mechanisms that collectively contribute to vascular smooth muscle (VSM) relaxation. It has been shown that B2-AR stimulation in cultured cells results in activation of extracellular signal-regulated kinase (ERK). As the functional relevance of this was not known, the aim of the current investigation was determine the role of ERK in beta-AR-mediated vasodilatation.
Isoprenaline-induced relaxation of porcine coronary artery (PCA) segments pre-contracted with the thromboxane mimetic U46619 was significantly enhanced by inhibition of ERK activation. Relaxations to the beta2-AR agonist salbutamol, but not those to the beta1-AR agonist xamoterol or the adenylyl cyclase activator forskolin, were also enhanced. The intermediate-conductance Ca2+-activated K+ (IKCa) channel blocker TRAM-34 prevented the enhancement of beta2-AR-mediated responses.
Taken together, the data indicate that ERK inhibits beta2-AR-mediated vasodilatation by interacting with a cyclic 3’, 5’-adenosine monophosphate-independent relaxation pathway involving K+ channels. This may occur through a direct regulatory action on the IKCa channel via phosphorylation.
Furthermore, the finding that increased ERK activation in a rat model of Type II diabetes was associated with significantly impaired beta-AR-mediated vasodilatation raises the possibility that ERK may represent a promising therapeutic target in the treatment of disease states characterised by abnormal vascular function. |
| first_indexed | 2025-11-14T18:30:28Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-12695 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T18:30:28Z |
| publishDate | 2012 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-126952025-02-28T11:20:50Z https://eprints.nottingham.ac.uk/12695/ The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation Uhiara, Chukwuemeka Obinna Beta-Adrenoceptors (B-ARs) mediate vasodilatation by activating various mechanisms that collectively contribute to vascular smooth muscle (VSM) relaxation. It has been shown that B2-AR stimulation in cultured cells results in activation of extracellular signal-regulated kinase (ERK). As the functional relevance of this was not known, the aim of the current investigation was determine the role of ERK in beta-AR-mediated vasodilatation. Isoprenaline-induced relaxation of porcine coronary artery (PCA) segments pre-contracted with the thromboxane mimetic U46619 was significantly enhanced by inhibition of ERK activation. Relaxations to the beta2-AR agonist salbutamol, but not those to the beta1-AR agonist xamoterol or the adenylyl cyclase activator forskolin, were also enhanced. The intermediate-conductance Ca2+-activated K+ (IKCa) channel blocker TRAM-34 prevented the enhancement of beta2-AR-mediated responses. Taken together, the data indicate that ERK inhibits beta2-AR-mediated vasodilatation by interacting with a cyclic 3’, 5’-adenosine monophosphate-independent relaxation pathway involving K+ channels. This may occur through a direct regulatory action on the IKCa channel via phosphorylation. Furthermore, the finding that increased ERK activation in a rat model of Type II diabetes was associated with significantly impaired beta-AR-mediated vasodilatation raises the possibility that ERK may represent a promising therapeutic target in the treatment of disease states characterised by abnormal vascular function. 2012-07-19 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/12695/1/Thesis_FINAL.pdf Uhiara, Chukwuemeka Obinna (2012) The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation. PhD thesis, University of Nottingham. ERK B-adrenoceptors porcine coronary artery statins |
| spellingShingle | ERK B-adrenoceptors porcine coronary artery statins Uhiara, Chukwuemeka Obinna The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title | The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title_full | The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title_fullStr | The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title_full_unstemmed | The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title_short | The role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| title_sort | role of extracellular signal-regulated kinase in beta-adrenoceptor-mediated vasodilatation |
| topic | ERK B-adrenoceptors porcine coronary artery statins |
| url | https://eprints.nottingham.ac.uk/12695/ |