Serotonin 5-HT1A receptor stimulates c-Jun N-terrninal kinase and induces apoptosis in Chinese hamster ovary fibroblasts

The 5-HTlA receptor is a prototypical member of the large and diverse scrotonin 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-HTlA 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-HTlA receptor stimulates JNK. JNK stimulation was Pertussis toxin-sensitive and was mediated by Rho family low molecular weight GTPases. The 5-HTlA 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-HTlA receptor stimulates both ERK-dependent anti-apoptotic pathways and JNK-dependent pro-apoptotic pathways in CHO cells. (c) 2006 Published by Elsevier B.V.