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

Jin O-Uchi, Kimiaki Komukai, Yoichiro Kusakari, Satoshi Morimoto, Makoto Kawai, Bong Sook Jhun, Stephen Hurst, Kenichi Hongo, Shey Shing Sheu, Satoshi Kurihara

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 Ca2+ current, Ca2+ transients and contractile force through phosphorylation of tyrosine residues in β1-adrenoceptor by PTK. Our results indicate that inhibition of β-adrenoceptor-mediated Ca2+ elevation by α1-adrenoceptor-PTK signaling serves as an important regulatory feedback mechanism when the catecholamine level increases to protect cardiomyocytes from cytosolic Ca2+ overload.

Original languageEnglish (US)
Pages (from-to)188-193
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume433
Issue number2
DOIs
StatePublished - Apr 2013
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Ms. N. Tomizawa, Ms. M. Nomura, Ms. Y. Natake, Mr. Y. Kimura and Dr. E. Fujiwara for their technical assistance. This study was supported by Japan Heart Foundation, Kato Memorial Bioscience Foundation, The Jikei University Research Fund, Irisawa Memorial Promotion Award, the Physiological Society of Japan (to J.O.-U.), NIH training grant (5T32AA007463-26) (to S.H.) a Grant-in Aid (22300130 and 23136515) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Vehicle Racing Commemorative Foundation (to S.K.).

Keywords

  • Adrenergic receptor
  • CAMP
  • G protein

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