TY - JOUR AU - Luo Da-li AU - Gao Jian AU - Lan Xiao-mei AU - Wang Gang AU - Wei Sheng AU - Xiao Rui-ping AU - Han Qi-de PY - 2016 TI - Role of inositol 1,4,5-trisphosphate receptors in α 1 -adrenergic receptor-induced cardiomyocyte hypertrophy JF - Acta Pharmacologica Sinica; Vol 27, No 7 (July 2006): Acta Pharmacologica Sinica(Special Issue on Calcium signaling) Y2 - 2016 KW - N2 - Aim: Intracellular Ca 2+ 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 (IP 3 Rs) in the mediation of cardiac intracellular Ca 2+ and hypertrophic growth remains elusive. Prior work with neonatal rat ventricular myocytes suggests that activation of IP 3 Rs may be linked to α 1 adrenergic receptor (α 1 AR) increased stereotyped Ca 2+ spark occurrence and global Ca 2+ oscillations. Thus, we hypothesized that Ca 2+ release through IP 3 Rs was necessary for α 1 AR-stimulated cardiac hypertrophy. Methods: We used myoinositol 1,4,5-trisphosphate hexakis (butyryloxymethyl) ester (IP 3 BM), a membrane-permeant ester of IP 3 , to activate IP 3 Rs directly, and Fluo 4/AM to measure intracellular Ca 2+ signaling. Results: IP 3 BM (10 μmol-L -1 ) mimicked the effects of phenylephrine, a selective agonist of α 1 AR, in increments in local Ca 2+ spark release (especially in the perinuclear area) and global Ca 2+ transient frequencies. More importantly, IP 3 R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C, abolished the IP 3 BM-induced Ca 2+ responses, and significantly suppressed α 1 AR-induced cardiomyocyte hypertrophy assayed by cell size, [ 3 H] leucine incorporation and atrial natriuretic factor gene expression, during sustained (48 h) phenylephrine stimulation. Conclusion: These results, therefore, provide cellular mechanisms that link IP 3 R signaling to α 1 AR-stimulated gene expression and cardiomyocyte hypertrophy. UR - http://www.chinaphar.com/article/view/4016