BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca(2+) concentration ([Ca(2+)]i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca(2+)]i in airway smooth muscle cells (ASMCs). METHODS: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. RESULTS: RT-PCR analysis showed that α2-7, β2, and β3-nAChR subunits are expressed in rat ASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca(2+)]i in cultured rat ASMCs. Acute application of nicotine evoked a rapid increase in [Ca(2+)]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 µM nicotine for 48 hours. Nicotine-induced Ca(2+) response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca(2+) responses induced by nicotine. CONCLUSION: These observations suggest that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca(2+) concentration ([Ca(2+)]i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca(2+)]i in airway smooth muscle cells (ASMCs). METHODS: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. RESULTS: RT-PCR analysis showed that α2-7, β2, and β3-nAChR subunits are expressed in ratASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca(2+)]i in cultured ratASMCs. Acute application of nicotine evoked a rapid increase in [Ca(2+)]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 µM nicotine for 48 hours. Nicotine-induced Ca(2+) response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca(2+) responses induced by nicotine. CONCLUSION: These observations suggest that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.
Authors: Niyati A Borkar; Benjamin Roos; Y S Prakash; Venkatachalem Sathish; Christina M Pabelick Journal: Arch Biochem Biophys Date: 2021-05-15 Impact factor: 4.114
Authors: Itsaso Garcia-Arcos; Patrick Geraghty; Nathalie Baumlin; Michael Campos; Abdoulaye Jules Dabo; Bakr Jundi; Neville Cummins; Edward Eden; Astrid Grosche; Matthias Salathe; Robert Foronjy Journal: Thorax Date: 2016-08-24 Impact factor: 9.139