Serotonin 5-HT1A receptor stimulates c-Jun N-terminal kinase and induces apoptosis in Chinese hamster ovary fibroblasts.
The 5-HT1A receptor is a prototypical member of the large and diverse serotonin receptor family. One key role of this receptor is to stimulate cell proliferation and differentiation via the extracellular signal regulated protein kinase (ERK) mitogen activated protein (MAP) kinase. There are few reports on the ability of the 5-HT1A receptor to modulate other MAP kinases such as c-Jun N-terminal kinase (JNK), which is activated by various extracellular stimuli, resulting in cell growth, differentiation, and programmed cell death. We report here for the first time that the 5-HT1A receptor stimulates JNK. JNK stimulation was Pertussis toxin-sensitive and was mediated by Rho family low molecular weight GTPases. The 5-HT1A receptor also increased apoptosis, which was mimicked by the MEK inhibitor PD98059, and blocked by the JNK inhibitor SP600125. These results suggest that the 5-HT1A receptor stimulates both ERK-dependent anti-apoptotic pathways and JNK-dependent pro-apoptotic pathways in CHO cells.
Turner
Justin H
JH
The Medical and Research Services of the Ralph H. Johnson Veterans Affairs Medical Center, Department of Medicine (Nephrology Division) of the Medical University of South Carolina, Charleston, SC 29425, USA.
Garnovskaya
Maria N
MN
Raymond
John R
JR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002843:Chromatin / Q000187:drug effects / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008970:Molecular Weight; D037342:Pertussis Toxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D002843:Chromatin; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020741:rho GTP-Binding Proteins