| First Author | Pera T | Year | 2015 |
| Journal | FASEB J | Volume | 29 |
| Issue | 10 | Pages | 4227-35 |
| PubMed ID | 26103985 | Mgi Jnum | J:230447 |
| Mgi Id | MGI:5760093 | Doi | 10.1096/fj.15-273094 |
| Citation | Pera T, et al. (2015) Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function. FASEB J 29(10):4227-35 |
| abstractText | Arrestins have been shown to regulate numerous G protein-coupled receptors (GPCRs) in studies employing receptor/arrestin overexpression in artificial cell systems. Which arrestin isoforms regulate which GPCRs in primary cell types is poorly understood. We sought to determine the effect of beta-arrestin-1 or beta-arrestin-2 inhibition or gene ablation on signaling and function of multiple GPCRs endogenously expressed in airway smooth muscle (ASM). In vitro [second messenger (calcium, cAMP generation)], ex vivo (ASM tension generation in suspended airway), and in vivo (invasive airway resistance) analyses were performed on human ASM cells and murine airways/whole animal subject to beta-arrestin-1 or -2 knockdown or knockout (KO). In both human and murine model systems, knockdown or KO of beta-arrestin-2 relative to control missense small interfering RNA or wild-type mice selectively increased (40-60%) beta2-adrenoceptor signaling and function. beta-arrestin-1 knockdown or KO had no effect on signaling and function of beta2-adrenoceptor or numerous procontractile GPCRs, but selectively inhibited M3 muscarinic acetylcholine receptor signaling ( approximately 50%) and function ( approximately 25% ex vivo, >50% in vivo) without affecting EC50 values. Arrestin subtypes differentially regulate ASM GPCRs and beta-arrestin-1 inhibition represents a novel approach to managing bronchospasm in obstructive lung diseases. |
