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  • Alpha1-adrenenoceptor stimulation inhibits cardiac excitation-contraction coupling through tyrosine phosphorylation of beta1-adrenoceptor.

Alpha1-adrenenoceptor stimulation inhibits cardiac excitation-contraction coupling through tyrosine phosphorylation of beta1-adrenoceptor.

Biochemical and biophysical research communications (2013-03-05)
Jin O-Uchi, Kimiaki Komukai, Yoichiro Kusakari, Satoshi Morimoto, Makoto Kawai, Bong Sook Jhun, Stephen Hurst, Kenichi Hongo, Shey-Shing Sheu, Satoshi Kurihara
ABSTRACT

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 β1-adrenoceptor is estimated to regulate Gs-protein binding affinity from crystal structure studies, but the signaling pathway leading to the phosphorylation of these residues is unknown. Here we show α1-adrenergic signaling inhibits β-adrenergically activated Ca(2+) current, Ca(2+) transients and contractile force through phosphorylation of tyrosine residues in β1-adrenoceptor by PTK. Our results indicate that inhibition of β-adrenoceptor-mediated Ca(2+) elevation by α1-adrenoceptor-PTK signaling serves as an important regulatory feedback mechanism when the catecholamine level increases to protect cardiomyocytes from cytosolic Ca(2+) overload.

MATERIALS
Product Number
Brand
Product Description

Supelco
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Sigma-Aldrich
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R-(-)-Phenylephrine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
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