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

In the present study, we report that somatostatin receptor 2 (SSTR2) plays a crucial role in modulation of beta(1)AR and beta(2)AR mediated signaling pathways that are associated with increased intracellular Ca2+ and cardiac complications. In H9c2 cells, SSTR2 colocalizes with beta(1)AR or beta(2)AR 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 PKC alpha and PKC beta was comparable to the basal condition, however SSTR2 agonist inhibits isoproterenol or formoterol induced PKC alpha and PKC beta 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. (C) 2014 Elsevier B.V. All rights reserved.