The muscarinic antagonist gallamine induces proliferation of airway smooth muscle cells regardless of the cell phenotype.
Pharmacol Rep
; 71(2): 225-232, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30785060
ABSTRACT
BACKGROUND:
Muscarinic receptor antagonists are a usual treatment for chronic airway diseases, with increased bronchoconstriction, like asthma and chronic obstructive pulmonary disease. These diseases are usually accompanied by airway remodeling, involving airway smooth muscle cell (ASMC) proliferation. The purpose of this study was to examine the effect of the muscarinic receptor modulator gallamine on rabbit tracheal ASMC proliferation.METHODS:
ASMCs were incubated with gallamine (1 nM-10 mM), atropine (1 fM-10 mM), and/or acetylcholine (1 nM-1 mM), in the presence or absence of FBS (1% or 10%). Cell proliferation was estimated by incorporation of radioactive thymidine, the Cell Titer AQueous One Solution method and cell number counting after Trypan blue exclusion. The mechanisms mediating cell proliferation were studied using the PI3K and MAPK inhibitors LY294002 (20 µM) and PD98059 (100 µM), respectively. Cell phenotype was studied by indirect immunofluorescence for α-actin, Myosin Heavy Chain and desmin.RESULTS:
ASMC incubation with the muscarinic receptor allosteric modulator gallamine or the muscarinic receptor antagonist atropine increased methyl-[3H]thymidine incorporation and cell number in a dose-dependent manner. ASMC proliferation was mediated via PI3K and MAPK activation and was transient. Gallamine antagonized the mitogenic effect of 1% FBS. Furthermore, gallamine had a similar effect on contractile ASMCs, without synergizing with or affecting acetylcholine induced proliferation, or altering the percentage of ASMCs expressing contractile phenotype marker proteins.CONCLUSIONS:
Gallamine, in the absence of any agonist, has a transient mitogenic effect on ASMCs, regardless of the cell phenotype, mediated by the PI3K and the MAPK signaling pathways.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antagonistas Muscarínicos
/
Miócitos de Músculo Liso
/
Proliferação de Células
/
Trietiodeto de Galamina
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Rep
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de publicação:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND