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Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptor-induced cardiomyocyte hypertrophy

  
@article{APS4016,
	author = {Da-li Luo and Jian Gao and Xiao-mei Lan and Gang Wang and Sheng Wei and Rui-ping Xiao and Qi-de Han},
	title = {Role of inositol 1,4,5-trisphosphate receptors in α1-adrenergic receptor-induced   cardiomyocyte hypertrophy},
	journal = {Acta Pharmacologica Sinica},
	volume = {27},
	number = {7},
	year = {2016},
	keywords = {},
	abstract = {Aim: Intracellular Ca2+ plays pivotal roles in diverse cellular functions, including gene transcription that underlies cardiac remodeling during stress responses. However, the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the mediation of cardiac intracellular Ca2+ and hypertrophic growth remains elusive. Prior work with neonatal rat ventricular myocytes suggests that activation of IP3Rs may be linked to α1 adrenergic receptor (α1 AR) increased stereotyped Ca2+ spark occurrence and global Ca2+ oscillations. Thus, we hypothesized that Ca2+ release through IP3Rs was necessary for α1 AR-stimulated cardiac hypertrophy.
Methods: We used myoinositol 1,4,5-trisphosphate hexakis (butyryloxymethyl) ester (IP3BM), a membrane-permeant ester of IP3, to activate IP3Rs directly, and Fluo 4/AM to measure intracellular Ca2+ signaling.
Results: IP3BM (10 μmol-L-1) mimicked the effects of phenylephrine, a selective agonist of α1AR, in increments in local Ca2+ spark release (especially in the perinuclear area) and global Ca2+ transient frequencies. More importantly, IP3R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C, abolished the IP3BM-induced Ca2+ responses, and significantly suppressed α1AR-induced cardiomyocyte hypertrophy assayed by cell size, [3H] leucine incorporation and atrial natriuretic factor gene expression, during sustained (48 h) phenylephrine stimulation.
Conclusion: These results, therefore, provide cellular mechanisms that link IP3R signaling to α1 AR-stimulated gene expression and cardiomyocyte hypertrophy.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4016}
}