The PGE2 receptor EP3 plays a positive role in the activation of hypothalamic-pituitary-adrenal axis and neuronal activity in the hypothalamus under immobilization stress.

Leyuan Lv, Dongying Bai, Yihong Ma, Kexin Liu, Yanbo Ma

Brain research bulletin 2021 Mar

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Prostaglandin E2 (PGE2) binds to four receptor subtypes (EP1, EP2, EP3 and EP4) and plays an important role in response to stress. However, the identity of the receptor(s) responsible for PGE2 regulation of neuronal activity and signaling through activation of the hypothalamic-pituitary-adrenal (HPA) axis under immobilization stress is unknown. The present study aimed to investigate the role of the hypothalamic PGE2 receptors in the activation of the HPA axis and neuronal activity in a rat model of stress. Stress was induced by immobilization of the animals, after which the stress-induced profile of PGE2 receptor signaling in the rat hypothalamus was determined by real-time polymerase chain reaction and immunohistochemistry. The effect of a selective EP3 receptor antagonist on corticosterone concentrations and c-Fos immunoreactivity was measured. Expression of EP2 and EP3 receptor genes, but not EP1 and EP4, was increased following immobilization stress. The EP3 receptor was localized to the paraventricular nucleus (PVN) of the hypothalamus, and the integrated density of the EP3 receptor was increased after immobilization stress. Rats given L-798,106, a selective antagonist of the EP3 receptor, showed significant attenuation of stress-increased serum corticosterone levels. EP3 antagonist also significantly suppressed the increase in the gene expression of c-Fos and the number of c-Fos-immunoreactive cells in the PVN of the hypothalamus following immobilization stress. These results suggest that immobilization stress may result in increased activation of the HPA axis and neuronal activity through regulating the function of the EP3 receptor. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Leyuan Lv, Dongying Bai, Yihong Ma, Kexin Liu, Yanbo Ma. The PGE2 receptor EP3 plays a positive role in the activation of hypothalamic-pituitary-adrenal axis and neuronal activity in the hypothalamus under immobilization stress. Brain research bulletin. 2021 Mar;168:45-51