Involvement of cAMP-dependent protein kinase and pertussis toxin-sensitive G-proteins in CGRP mediated JNK activation in human neuroblastoma cell line
Neuropeptides(2000)
摘要
Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects, which include positive inotropic and chronotropic actions, systemic vasodilation, and hypotension in animal and human studies. Human neuroblastoma cells (SK-N-MC) have been used as a model system to study the CGRP receptors and downstream signaling pathways. This investigation was undertaken to study the role of CGRP in the activation of mitogen-activated protein kinases. While exposure of these cells to CGRP had no significant effect on ERK-1 or p38 MAP kinases, JNK activity was stimulated by CGRP in a time- and concentration-dependent fashion. CGRP-mediated JNK-activation was inhibited by CGRP receptor antagonist, CGRP8–37, confirming that this is a receptor-mediated event. In addition, pretreatment of the cells with H-89, protein kinase A inhibitor or pertussis toxin greatly attenuated CGRP-mediated JNK activation suggesting the requirement of cAMP-dependent protein kinase activation and involvement of pertussis toxin-sensitive G-protein in CGRP-mediated JNK activation.
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关键词
map kinase,protein kinase a,signaling pathway,cell line,pertussis toxin,camp dependent protein kinase,calcitonin gene related peptide,mitogen activated protein kinase,g protein
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