Involvement of cAMP-dependent protein kinase and pertussis toxin-sensitive G-proteins in CGRP mediated JNK activation in human neuroblastoma cell line.
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.
Disa
J
J
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406-0939, USA.
Parameswaran
N
N
Nambi
P
P
Aiyar
N
N
D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009447:Neuroblastoma; D037342:Pertussis Toxin; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D016755:Proto-Oncogene Proteins c-jun; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D015740:Calcitonin Gene-Related Peptide