caa a22 4500 606236627 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2278-x doi (NATIONALLICENCE)springer-10.1007/s11010-014-2278-x Role of group I metabotropic glutamate receptors, mGluR1/mGluR5, in connexin43 phosphorylation and inhibition of gap junctional intercellular communication in H9c2 cardiomyoblast cells [Elektronische Daten] [Fei Xie, Shao-lei Yi, Li Hao, Yun Zhang, Jing-quan Zhong] Group I metabotropic glutamate receptors, mGluR1 and mGluR5, are associated with sympathetic nerve activity. Sympathetic nerve stimulation exerts a crucial effect on modulating phosphorylation status and distribution of connexin43 (Cx43) in rat heart. Hence, mGluR1 and mGluR5 have an indirect effect on regulating the function of gap junction channels, which is affected by the availability of Cx43 protein. Additionally, it has been demonstrated that mGluR1/5 are present in ventricular myocardium in particular intercalated disks where Cx43 is the principal component of ventricular gap junction channels. We, therefore, hypothesized that mGluR1/5 might regulate Cx43 phosphorylation and gap junctional intercellular communication (GJIC) directly, independent of sympathetic nerve stimulation. After documenting the presence of mGluR1 and mGluR5 in H9c2 cardiomyoblast cells, addition of the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) induced Cx43 phosphorylation and GJIC inhibition in both concentration- and time-dependent manner. The effects of DHPG were abolished by the mGluR1 antagonist LY367385 and the specific inhibitor of MEK1, PD98059 which also reduced phosphorylation of extracellular-signal-regulated protein kinase 1/2 (ERK1/2); but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride or the selective inhibitor of protein kinase C (PKC). In conclusion, in H9c2 cardiomyoblast cells mGluR1 increases Cx43 phosphorylation level and suppresses GJIC involving ERK1/2 but not PKC. Springer Science+Business Media New York, 2014 Metabotropic glutamate receptor nationallicence Gap junction intercellular communication nationallicence Connexin43 nationallicence Phosphorylation nationallicence ERK1/2 nationallicence PKC nationallicence Xie Fei Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut Yi Shao-lei Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut Hao Li Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut Zhang Yun Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut Zhong Jing-quan Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 213-222 0300-8177 400:1-2<213 2015 400 11010 https://doi.org/10.1007/s11010-014-2278-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2278-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xie Fei Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut NATIONALLICENCE 700 1- Yi Shao-lei Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut NATIONALLICENCE 700 1- Hao Li Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut NATIONALLICENCE 700 1- Zhang Yun Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut NATIONALLICENCE 700 1- Zhong Jing-quan Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health,Department of Cardiology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, 250012, Jinan, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 213-222 0300-8177 400:1-2<213 2015 400 11010