Alpha(1)-adrenenoceptor stimulation inhibits cardiac excitation-contraction coupling through tyrosine phosphorylation of beta(1)-adrenoceptor

作者：O Uchi Jin^*; Komukai Kimiaki; Kusakari Yoichiro; Morimoto Satoshi; Kawai Makoto; Jhun Bong Sook; Hurst Stephen; Hongo Kenichi; Sheu Shey Shing; Kurihara Satoshi

来源：Biochemical and Biophysical Research Communications, 2013, 433(2): 188-193.

DOI：10.1016/j.bbrc.2013.02.072

• Adrenergic receptor
• L-type Ca2+ channel
• cAMP
• G protein

Adrenoceptor stimulation is a key determinant of cardiac excitation-contraction coupling mainly through the activation of serine/threonine kinases. However, little is known about the role of protein tyrosine kinases (PTKs) activated by adrenergic signaling on cardiac excitation-contraction coupling. A cytoplasmic tyrosine residue in beta(1)-adrenoceptor is estimated to regulate G(s)-protein binding affinity from crystal structure studies, but the signaling pathway leading to the phosphorylation of these residues is unknown. Here we show alpha(1)-adrenergic signaling inhibits beta-adrenergically activated Ca2+ current, Ca2+ transients and contractile force through phosphorylation of tyrosine residues in beta(1)-adrenoceptor by PTK. Our results indicate that inhibition of beta-adrenoceptor-mediated Ca2+ elevation by alpha(1)-adrenoceptor-PTK signaling serves as an important regulatory feedback mechanism when the catecholamine level increases to protect cardiomyocytes from cytosolic Ca2+ overload.

• 出版日期2013-4-5