title: Role of group I metabotropic glutamate receptors, mGluR1/mGluR5, in connexin43 phosphorylation and inhibition of gap junctional intercellular communication in H9c2 cardiomyoblast cells.
abstract: 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.
authors.affiliation: 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, Jinan, 250012, China, xiefei890228@sina.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.forename: Shao-lei
authors.initials: SL
authors.lastname: Yi
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing-quan
authors.initials: JQ
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001565:Benzoates / Q000008:administration & dosage; D002450:Cell Communication / Q000235:genetics; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000008:administration & dosage / Q000031:analogs & derivatives; D032446:Myoblasts / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism
chemical_list: D001565:Benzoates; D018031:Connexin 43; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C079694:alpha-methyl-4-carboxyphenylglycine; D008734:Methoxyhydroxyphenylglycol; D048369:MAP Kinase Kinase 1; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol