Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways.
In allergic asthma Beta 2 adrenergic receptors (β2ARs) are important mediators of bronchorelaxation and, paradoxically, asthma development. This contradiction is likely due to the activation of dual signaling pathways that are downstream of G proteins or β-arrestins. Our group has recently shown tha...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4319755?pdf=render |
| _version_ | 1817989365363638272 |
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| author | Akhil Hegde Ryan T Strachan Julia K L Walker |
| author_facet | Akhil Hegde Ryan T Strachan Julia K L Walker |
| author_sort | Akhil Hegde |
| collection | DOAJ |
| description | In allergic asthma Beta 2 adrenergic receptors (β2ARs) are important mediators of bronchorelaxation and, paradoxically, asthma development. This contradiction is likely due to the activation of dual signaling pathways that are downstream of G proteins or β-arrestins. Our group has recently shown that β-arrestin-2 acts in its classical role to desensitize and constrain β2AR-induced relaxation of both human and murine airway smooth muscle. To assess the role of β-arrestins in regulating β2AR function in asthma, we and others have utilized β-arrestin-1 and -2 knockout mice. However, it is unknown if genetic deletion of β-arrestins in these mice influences β2AR expression in the airways. Furthermore, there is lack of data on compensatory expression of βAR subtypes when either of the β-arrestins is genetically deleted, thus necessitating a detailed βAR subtype expression study in these β-arrestin knockout mice. Here we standardized a radioligand binding methodology to characterize and quantitate βAR subtype distribution in the airway smooth muscle of wild-type C57BL/6J and β-arrestin-1 and β-arrestin-2 knockout mice. Using complementary competition and single-point saturation binding assays we found that β2ARs predominate over β1ARs in the whole lung and epithelium-denuded tracheobronchial smooth muscle of C57BL/6J mice. Quantification of βAR subtypes in β-arrestin-1 and β-arrestin-2 knockout mouse lung and epithelium-denuded tracheobronchial tissue showed that, similar to the C57BL/6J mice, both knockouts display a predominance of β2AR expression. These data provide further evidence that β2ARs are expressed in greater abundance than β1ARs in the tracheobronchial smooth muscle and that loss of either β-arrestin does not significantly affect the expression or relative proportions of βAR subtypes. As β-arrestins are known to modulate β2AR function, our analysis of βAR subtype expression in β-arrestin knockout mice airways sets a reference point for future studies exploiting these knockout mice in various disease models including asthma. |
| first_indexed | 2024-04-14T00:46:04Z |
| format | Article |
| id | doaj.art-5d663c15f7744fcab28ddd4e063387bc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T00:46:04Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5d663c15f7744fcab28ddd4e063387bc2022-12-22T02:22:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011645810.1371/journal.pone.0116458Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways.Akhil HegdeRyan T StrachanJulia K L WalkerIn allergic asthma Beta 2 adrenergic receptors (β2ARs) are important mediators of bronchorelaxation and, paradoxically, asthma development. This contradiction is likely due to the activation of dual signaling pathways that are downstream of G proteins or β-arrestins. Our group has recently shown that β-arrestin-2 acts in its classical role to desensitize and constrain β2AR-induced relaxation of both human and murine airway smooth muscle. To assess the role of β-arrestins in regulating β2AR function in asthma, we and others have utilized β-arrestin-1 and -2 knockout mice. However, it is unknown if genetic deletion of β-arrestins in these mice influences β2AR expression in the airways. Furthermore, there is lack of data on compensatory expression of βAR subtypes when either of the β-arrestins is genetically deleted, thus necessitating a detailed βAR subtype expression study in these β-arrestin knockout mice. Here we standardized a radioligand binding methodology to characterize and quantitate βAR subtype distribution in the airway smooth muscle of wild-type C57BL/6J and β-arrestin-1 and β-arrestin-2 knockout mice. Using complementary competition and single-point saturation binding assays we found that β2ARs predominate over β1ARs in the whole lung and epithelium-denuded tracheobronchial smooth muscle of C57BL/6J mice. Quantification of βAR subtypes in β-arrestin-1 and β-arrestin-2 knockout mouse lung and epithelium-denuded tracheobronchial tissue showed that, similar to the C57BL/6J mice, both knockouts display a predominance of β2AR expression. These data provide further evidence that β2ARs are expressed in greater abundance than β1ARs in the tracheobronchial smooth muscle and that loss of either β-arrestin does not significantly affect the expression or relative proportions of βAR subtypes. As β-arrestins are known to modulate β2AR function, our analysis of βAR subtype expression in β-arrestin knockout mice airways sets a reference point for future studies exploiting these knockout mice in various disease models including asthma.http://europepmc.org/articles/PMC4319755?pdf=render |
| spellingShingle | Akhil Hegde Ryan T Strachan Julia K L Walker Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. PLoS ONE |
| title | Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. |
| title_full | Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. |
| title_fullStr | Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. |
| title_full_unstemmed | Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. |
| title_short | Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. |
| title_sort | quantification of beta adrenergic receptor subtypes in beta arrestin knockout mouse airways |
| url | http://europepmc.org/articles/PMC4319755?pdf=render |
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