Somatostatin receptor-2 negatively regulates β-adrenergic receptor mediated Ca2+ dependent signaling pathways in H9c2 cells

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1843; no. 4; pp. 735 - 745
• Main Authors: Somvanshi, Rishi K., Zou, Shenglong, Qiu, Xiaofan, Kumar, Ujendra
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-04-2014
• Subjects: Adrenergic receptor; H9c2 cell; Hypertrophy; Signaling; Somatostatin receptor 2; AC; β-AR; PKA; PKC; cAMP; SSTR2; H9c2 cell; NFAT; Signaling; Ca2; Somatostatin receptor 2; Adrenergic receptor; FSK; LVH; Hypertrophy
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2014.01.002

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 Ca2+ 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 Ca2+ associated signaling pathways attributed to cardiac hypertrophy.
•In H9c2 cells, SSTR2 colocalizes with β-ARs and expressed in β-AR immunoprecipitate.•SSTR2 modulates β1 and β2AR mediated Ca2+ associated signaling pathways including cAMP, PKC, calcineurin and NFAT.•SSTR2 activation attenuates β-AR mediated changes in cell size and total protein content.•SSTR2 can be targeted as potential therapeutic intervention in regulating factors contributing to cardiac complications.