Calcitonin gene related peptide (CGRP) inhibits norepinephrine induced apoptosis in cultured rat cardiomyocytes not via PKA or PKC pathways.

Evidence showed overrelease of norepinephrine can induce apoptosis in ventricle myocytes. Calcitonin gene related peptide and norepinephrine could be simultaneously up-regulated in early time of acute myocardial ischemia, suggesting a co-participation of calcitonin gene related peptide and norepinephrine in the pathology. In this study, we investigated a potential anti-apoptotic effect of calcitonin gene related peptide on myocardial apoptosis induced by norepinephrine and its link with the protein kinase A (PKA) or protein kinase C (PKC) pathway in cultured neonatal rat cardiomyocytes. Cultured cardiomyocytes were exposed to one of the treatments, separately: (1) 3 ml DMEM culture medium, (2) norepinephrine (10(-5)mol/l), (3) H89 (3 x 10(-5)mol/l), a specific PKA inhibitor, with norepinephrine (10(-5)mol/l), (4) calcitonin gene related peptide at a range of concentrations (10(-9)mol/l, 10(-8)mol/l and 10(-7)mol/l) with norepinephrine (10(-5)mol/l) and (5) calcitonin gene related peptide (10(-8)mol/l) with norepinephrine (10(-5)mol/l)+CGRP(8-7) (10(-7)mol/l), a specific antagonist of calcitonin gene related peptide receptor. Then, apoptosis rate and the activity of PKA and PKC were examined. The dose of norepinephrine induced a marked increase in apoptosis of the myocytes (31+/-2%), compared to the control (17+/-4%, p<0.05). The pro-apoptotic effect of norepinephrine was attenuated by H89 (3 x 10(-5)mol/l) or by calcitonin gene related peptide which could be completely reversed by CGRP(8-37). The activities of PKA and PKC were increased by norepinephrine but no difference in the activities of PKA and PKC was detected in the presence and absence of co-treatment with calcitonin gene related peptide (10(-8)mol/l). Calcitonin gene related peptide inhibits norepinephrine induced apoptosis in cultured cardiomyocytes, which is mediated by CGRP receptor but unlikely to be mediated by PKA or PKC pathway. (c) 2010 Elsevier Ireland Ltd. All rights reserved.