| First Author | Hegde A | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 2 | Pages | e0116458 |
| PubMed ID | 25658948 | Mgi Jnum | J:229044 |
| Mgi Id | MGI:5750268 | Doi | 10.1371/journal.pone.0116458 |
| Citation | Hegde A, et al. (2015) Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways. PLoS One 10(2):e0116458 |
| abstractText | In allergic asthma Beta 2 adrenergic receptors (beta2ARs) 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 beta-arrestins. Our group has recently shown that beta-arrestin-2 acts in its classical role to desensitize and constrain beta2AR-induced relaxation of both human and murine airway smooth muscle. To assess the role of beta-arrestins in regulating beta2AR function in asthma, we and others have utilized beta-arrestin-1 and -2 knockout mice. However, it is unknown if genetic deletion of beta-arrestins in these mice influences beta2AR expression in the airways. Furthermore, there is lack of data on compensatory expression of betaAR subtypes when either of the beta-arrestins is genetically deleted, thus necessitating a detailed betaAR subtype expression study in these beta-arrestin knockout mice. Here we standardized a radioligand binding methodology to characterize and quantitate betaAR subtype distribution in the airway smooth muscle of wild-type C57BL/6J and beta-arrestin-1 and beta-arrestin-2 knockout mice. Using complementary competition and single-point saturation binding assays we found that beta2ARs predominate over beta1ARs in the whole lung and epithelium-denuded tracheobronchial smooth muscle of C57BL/6J mice. Quantification of betaAR subtypes in beta-arrestin-1 and beta-arrestin-2 knockout mouse lung and epithelium-denuded tracheobronchial tissue showed that, similar to the C57BL/6J mice, both knockouts display a predominance of beta2AR expression. These data provide further evidence that beta2ARs are expressed in greater abundance than beta1ARs in the tracheobronchial smooth muscle and that loss of either beta-arrestin does not significantly affect the expression or relative proportions of betaAR subtypes. As beta-arrestins are known to modulate beta2AR function, our analysis of betaAR subtype expression in beta-arrestin knockout mice airways sets a reference point for future studies exploiting these knockout mice in various disease models including asthma. |
