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Cholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptor
Author(s) -
Wu Jenny C.F.,
Chruscinski Andrzej,
De Jesus Perez Vinicio A.,
Singh Harvir,
Pitsiouni Maria,
Rabinovitch Marlene,
Utz Paul J.,
Cooke John P.
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22270
Subject(s) - angiogenesis , nicotine , nicotinic agonist , cholinergic , microbiology and biotechnology , nicotinic acetylcholine receptor , acetylcholine receptor , endothelial stem cell , biology , cancer research , pharmacology , chemistry , receptor , endocrinology , neuroscience , biochemistry , in vitro
Abstract Pathological angiogenesis contributes to tobacco‐related diseases such as malignancy, atherosclerosis and age‐related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except α 2 , α 4 , γ, and δ in four different types of ECs. Using siRNA methodology, we found that the α 7 nAChR plays a dominant role in nicotine‐induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine‐activated EC functions (proliferation, survival, migration, and tube formation). The α 9 and α 7 nAChRs have opposing effects on nicotine‐induced cell proliferation and survival. Our studies reveal a critical role for the α 7 nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis. J. Cell. Biochem. 108: 433–446, 2009. © 2009 Wiley‐Liss, Inc.