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EnglishOBJECTIVE: This study was aimed at investigating whether the β2 -adrenoceptor agonist, salbutamol, could modulate RhoA activation in normal and homologously desensitized bronchial smooth muscle cells (BSMC). METHODS: Serum-starved BSMCs were stimulated with the Rho-activating compound calpeptin in the presence or absence of salbutamol, the Epac activator, 8-pCPT-2'-O-Me-cAMP, or the site-selective activator of cAMP-dependent protein kinase A (PKA), 6-Bnz-cAMP. Activated RhoA was assessed by immunocytochemical detection and by RhoA G-LISA assay. KEY FINDINGS: Stimulation with calpeptin caused translocation of RhoA from cytosol to plasma membrane, a condition required for the functional coupling of RhoA with its cellular targets. Pretreatment with salbutamol 10 μm for 15 min was found to block calpeptin-induced activation of RhoA in normal, but not in homologously desensitized cells. Pretreatment of calpeptin-stimulated BSMC with 8-pCPT-2'-O-Me-cAMP or 6-Bnz-cAMP could reproduce the effect of salbutamol. CONCLUSIONS: These findings demonstrated that salbutamol inhibits RhoA activation in human BSMC through β2 -adrenoceptor/Epac/PKA pathway. An important pharmacological implication of these finding is the possible contribution of RhoA pathway to the molecular mechanism involved in airway smooth muscle relaxation caused by acute/chronic exposure to β2-adrenoceptor agonists.
Salbutamol inhibits RhoA activation in normal but not in desensitized bronchial smooth muscle cells / Fogli, Stefano; Stefanelli, Fabio; Battolla, Barbara; Bianchi, Francesco; Breschi, Maria C; Mattii, Letizia. - In: JOURNAL OF PHARMACY AND PHARMACOLOGY. - ISSN 0022-3573. - ELETTRONICO. - (2015), pp. n/a-n/a.
| Autori interni: | |
| Autori: | Fogli, Stefano; Stefanelli, Fabio; Battolla, Barbara; Bianchi, Francesco; Breschi, Maria C; Mattii, Letizia |
| Titolo: | Salbutamol inhibits RhoA activation in normal but not in desensitized bronchial smooth muscle cells |
| Anno del prodotto: | 2015 |
| Digital Object Identifier (DOI): | 10.1111/jphp.12444 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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