Abstract
Orexin-A is an important neuropeptide involved in the regulation of feeding, arousal, energy consuming, and reward seeking in the body. The effects of orexin-A have widely studied in neurons but not in astrocytes. Here, we report that OX1R and OX2R are expressed in cultured rat astrocytes. Orexin-A stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and then induced the migration of astrocytes via its receptor OX1R but not OX2R. Orexin-A-induced ERK1/2 phosphorylation and astrocytes migration are Ca2+-dependent, since they could be inhibited by either chelating the extracellular Ca2+ or blocking the pathway of store-operated calcium entry (SOCE). Furthermore, both non-selective protein kinase C (PKC) inhibitor and PKCα selective inhibitor, but not PKCδ inhibitor, prevented the increase in ERK1/2 phosphorylation and the migration of astrocytes, indicating that the Ca2+-dependent PKCα acts as the downstream of the OX1R activation and mediates the orexin-A-induced increase in ERK1/2 phosphorylation and cell migration. In conclusion, these results suggest that orexin-A can stimulate ERK1/2 phosphorylation and then facilitate the migration of astrocytes via PLC-PKCα signal pathway, providing new knowledge about the functions of the OX1R in astrocytes.
Highlights
Orexins, known as hypocretins, are a pair of neuropeptides that first discovered in a specific population of neurons in the lateral hypothalamic area (LHA) [1,2], a region of the brain implicated in feeding, arousal, and motivated behavior
It had a maximal effect at 10 nM and 24 h treatment (Fig. 1A–B), suggesting that orexin-A could promote the migration of cultured rat astrocytes
Previous study have reported that orexin-A promotes cAMP synthesis in astrocytes via orexin type 1 receptor (OX1R) [9], but they do not demonstrate whether orexin receptors express in astrocytes
Summary
Known as hypocretins, are a pair of neuropeptides that first discovered in a specific population of neurons in the lateral hypothalamic area (LHA) [1,2], a region of the brain implicated in feeding, arousal, and motivated behavior. Orexin-A (hypocretin-1) and orexin-B (hypocretin-2) are derivatives from a common precursor, prepro-orexin [3]. They exert their actions via interaction with two closely related GPCRs called orexin type 1 receptor (OX1R) and 2 (OX2R) [4]. OX1R has greater affinity to orexin-A than orexin-B by 1 order of magnitude. OX2R has similar affinity for both orexin-A and orexin-B [5]. The bulk of evidence, obtained in a Chinese hamster ovary (CHO) cell line stably expressing OX1R and/or OX2R, indicates that activation of both receptors increases intracellular Ca2+ concentration [6,7]. Little is known about the intracellular events set off by orexins in astrocytes
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