title: Somatostatin receptor-2 negatively regulates β-adrenergic receptor mediated Ca(2+) dependent signaling pathways in H9c2 cells.
abstract: In the present study, we report that somatostatin receptor 2 (SSTR2) plays a crucial role in modulation of β1AR and β2AR mediated signaling pathways that are associated with increased intracellular Ca(2+) and cardiac complications. In H9c2 cells, SSTR2 colocalizes with β1AR or β2AR in receptor specific manner. SSTR2 selective agonist inhibits isoproterenol and formoterol stimulated cAMP formation and PKA phosphorylation in concentration dependent manner. In the presence of SSTR2 agonist, the expression of PKCα and PKCβ was comparable to the basal condition, however SSTR2 agonist inhibits isoproterenol or formoterol induced PKCα and PKCβ expression, respectively. Furthermore, the activation of SSTR2 not only inhibits calcineurin expression and its activity, but also blocks NFAT dephosphorylation and its nuclear translocation. SSTR2 selective agonist abrogates isoproterenol mediated increase in cell size and protein content (an index of hypertrophy). Taken together, the results described here provide direct evidence in support of cardiac protective role of SSTR2 via modulation of Ca(2+) associated signaling pathways attributed to cardiac hypertrophy.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Rishi K
authors.initials: RK
authors.lastname: Somvanshi
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Zou
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T1Z3, Canada. Electronic address: ujkumar@mail.ubc.ca.
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects*; D064546:Protein Kinase C beta / Q000096:biosynthesis / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000819:agonists / Q000378:metabolism
chemical_list: D004983:Ethanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D000242:Cyclic AMP; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D007545:Isoproterenol; D002118:Calcium; D000068759:Formoterol Fumarate
keywords: Adrenergic receptor; H9c2 cell; Hypertrophy; Signaling; Somatostatin receptor 2