PMID- 24377382
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140123
LR  - 20240318
IS  - 1939-4551 (Print)
IS  - 1939-4551 (Electronic)
IS  - 1939-4551 (Linking)
VI  - 6
IP  - 1
DP  - 2013 Dec 30
TI  - M2 Muscarinic acetylcholine receptor modulates rat airway smooth muscle cell 
      proliferation.
PG  - 22
LID - 10.1186/1939-4551-6-22 [doi]
AB  - Airways chronic inflammatory conditions in asthma and COPD are characterized by 
      tissue remodeling, being smooth muscle hyperplasia, the most important feature. 
      Non-neuronal and neuronal Acetylcholine acting on muscarinic receptors (MAChRs) 
      has been postulated as determinant of tissue remodeling in asthma and COPD by 
      promoting proliferation and phenotypic changes of airway smooth muscle cells 
      (ASMC). The objective was to evaluate proliferative responses to muscarinic 
      agonist as carbamylcholine (Cch) and to identify the MAchR subtype involved. ASMC 
      were isolated from tracheal fragments of Sprague-Dawley rats by enzymatic 
      digestion. Proliferation assays were performed by MTS-PMS method. Viability was 
      confirmed by trypan blue exclusion method. Mitogens as, epidermal growth factor 
      (EGF), Tumor necrosis factor-alpha (TNF-alpha) and fetal bovine serum (FBS) increased 
      ASMC proliferation (p < 0.05, n = 5). Cch alone increased ASMC proliferation at 
      24 and 48 hrs. However, combination of Cch with other mitogens exhibited a dual 
      effect, synergistic proliferation effect in the presence of EGF (5 ng/mL) and 5% 
      FBS and inhibiting the proliferation induced by 10% FBS, EGF (10 ng/mL) and TNF-alpha 
      (10 ng/mL). To determine the MAChR subtype involved in these biological 
      responses, a titration curve of selective muscarinic antagonists were performed. 
      The Cch stimulatory and inhibitory effects on ASCM proliferation was blocked by 
      AF-DX-116 (M2AChR selective antagonist), in greater proportion than 4-DAMP 
      (M3AChR selective antagonist), suggesting that the modulation of muscarinic 
      agonist-induced proliferation is M2AChR mediated responses. Thus, M2AChR can 
      activate multiple signal transduction systems and mediate both effects on ASMC 
      proliferation depending on the plethora and variable airway microenvironments 
      existing in asthma and COPD.
FAU - Placeres-Uray, Fabiola A
AU  - Placeres-Uray FA
FAU - Febres-Aldana, Christopher A
AU  - Febres-Aldana CA
FAU - Fernandez-Ruiz, Ruth
AU  - Fernandez-Ruiz R
FAU - Gonzalez de Alfonzo, Ramona
AU  - Gonzalez de Alfonzo R
FAU - Lippo de Becemberg, Itala A
AU  - Lippo de Becemberg IA
FAU - Alfonzo, Marcelo J
AU  - Alfonzo MJ
AD  - Seccion de Biomembranas, Instituto de Medicina Experimental, Facultad de 
      Medicina, Universidad Central de Venezuela (U,C,V), Caracas, Venezuela. 
      hmag5@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20131230
PL  - United States
TA  - World Allergy Organ J
JT  - The World Allergy Organization journal
JID - 101481283
PMC - PMC3898804
EDAT- 2014/01/01 06:00
MHDA- 2014/01/01 06:01
PMCR- 2013/01/01
CRDT- 2014/01/01 06:00
PHST- 2013/07/10 00:00 [received]
PHST- 2013/12/17 00:00 [accepted]
PHST- 2014/01/01 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/01/01 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - S1939-4551(19)30646-5 [pii]
AID - 1939-4551-6-22 [pii]
AID - 10.1186/1939-4551-6-22 [doi]
PST - epublish
SO  - World Allergy Organ J. 2013 Dec 30;6(1):22. doi: 10.1186/1939-4551-6-22.