Endothelin promotes neurite elongation by a mechanism dependent on c-Jun N-terminal kinase.
Endothelin (ET), which is known as a vasoconstrictive peptide, is associated with a lot of biological functions. Although endothelin receptors are expressed in the central nervous system (CNS), little is known about the effects of endothelin on neuronal function. In this study, we reported that endothelins elongate cortical neurites via the endothelin A receptor. All the endothelin isoforms tested, endothelin-1, endothelin-2, and endothelin-3, promoted neurite elongation. ET-1-induced neurite elongation was specifically inhibited by treatment with BQ123, an antagonist for the endothelin A receptor. In addition, inhibition of ET-1-induced c-Jun N-terminal kinase (JNK) activation by treatment with SP600125, a JNK inhibitor, also prevented the ET-1-mediated promotion of neurite elongation. Thus, endothelin induces cortical neurite elongation through the endothelin A receptor by a mechanism dependent on JNK.
Uesugi
Noriko
N
Department of Molecular Neuroscience, Graduate school of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Muramatsu
Rieko
R
Yamashita
Toshihide
T
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D044022:Receptor, Endothelin A / Q000502:physiology
D016232:Endothelins; D044022:Receptor, Endothelin A; D048031:JNK Mitogen-Activated Protein Kinases