title: Calcitonin gene related peptide (CGRP) inhibits norepinephrine induced apoptosis in cultured rat cardiomyocytes not via PKA or PKC pathways.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Zhao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine