title: Nicotine elevated intracellular Ca²⁺ in rat airway smooth muscle cells via activating and up-regulating α7-nicotinic acetylcholine receptor.
abstract: 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.
  
  
  CONCLUSIONS
  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: State Key Lab of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors: Yongliang
authors: Y
authors: Jiang
authors: Aiguo
authors: A
authors: Dai
authors: Yumin
authors: Y
authors: Zhou
authors: Gongyong
authors: G
authors: Peng
authors: Guoping
authors: G
authors: Hu
authors: Bing
authors: B
authors: Li
authors: James S K
authors: JS
authors: Sham
authors: Pixin
authors: P
authors: Ran
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000096:biosynthesis*
chemical_list: D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D002118:Calcium