Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 762, Issue -, Pages 459-463Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2015.06.013
Keywords
GPR40/FFA1; PC2; beta-endorphin; Antinociception
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [24592364]
- Grants-in-Aid for Scientific Research [24592364] Funding Source: KAKEN
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Previous studies have shown that the administration of docosahexaenoic acid (DHA) or GW9508, a GPR40/FFA1 (free fatty acid receptor) agonist, facilitates beta-endorphin release in the arcuate nucleus of the hypothalamus in mice. However, the mechanisms mediating (beta-endorphin release induced by GPR40/FFA1 agonists remain unknown. In this study, we focused on the changes in expression of hypothalamic prohormone convertase (PC) 2, which is a calcium-dependent subtilisin-related proteolytic enzyme. The intracerebroventricular injection of DHA or GW9508 significantly increased PC2 protein expression in the hypothalamus. This increase in PC2 expression was inhibited by pretreatment with GW1100, a GPR40/FFA1 antagonist. Furthermore, PC2 protein expression gradually increased over time after complete Freund's adjuvant. These increase in PC2 expression were inhibited by pretreatment with GW1100. However, GW1100 by itself had no effect on PC2 levels. Taken together, our findings suggest that activation of the hypothalamic GPR40/FFA1 signaling pathway may regulate beta-endorphin release via PC2, and regulate the endogenous pain control system. (C) 2015 Elsevier B.V. All rights reserved.
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