Ghrelin (rat)

Ghrelin (rat) is an endogenous brain-gut peptide secreted from rat stomach tissue, composed of 28 amino acids, and acts as an agonist of the growth hormone secretagogue receptor (GHS-R1a). Ghrelin can promote pituitary growth hormone release by activating GHS-R1a and its downstream cAMP/Ca²⁺ signaling pathway, and act on hypothalamic NPY/AgRP neurons to stimulate food intake, regulate energy balance, gastrointestinal motility, and glucose metabolic homeostasis. Ghrelin can be used in research related to obesity, metabolic syndrome, cachexia, gastrointestinal and cardiovascular diseases^[1-4].

In vitro, Ghrelin (0–30nM) was applied to rat C6 glioma cells and human U251 glioma cells for 5min to 24h. Ghrelin upregulated GHS-R expression, activated CaMKII, AMPK, and NF-κB signaling pathways, promoted IKKα/β, IκBα, and p65 Ser536 phosphorylation, enhanced NF-κB-DNA binding activity and κB transcriptional activity. Ghrelin increased glioma cell migration ability^[5]. Ghrelin (0.01nM to 1μM) was applied to rat pancreatic islets and CRI-D2 cells for 24h. Ghrelin significantly downregulated KiSS-1 and KissR mRNA transcription, and inhibited insulin secretion from pancreatic islets and CRI-D2 cells^[6].

In vivo, Ghrelin (300nmol/kg) combined with paclitaxel (2mg/kg) was intraperitoneally injected into wild-type C57BL/6J mice, Ghrelin-null mice, and growth hormone secretagogue receptor-null mice for 5 consecutive days. Ghrelin alleviated paclitaxel-induced mechanical and thermal hyperalgesia, prevented the loss of small unmyelinated intraepidermal nerve fibers, reduced plasma levels of 8-isoprostane, malondialdehyde, and nitric oxide, and upregulated the mRNA expression of mitochondrial antioxidant proteins UCP2, SOD2, and mitochondrial biogenesis regulator PGC-1α in dorsal root ganglia^[7]. Ghrelin (3nmol/mouse; single injection) was administered via the third ventricle or intraperitoneally into male ddy mice, followed by tail clip and starvation stress interventions. Ghrelin induced anxiety-like behavior in the elevated plus maze test and upregulated hypothalamic CRH mRNA expression^[8].

References:
[1] Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9;402(6762):656-60.
[2] Chung H, Choi J, Park S. Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation. Endocr J. 2018 Jan 30;65(1):63-73.
[3] Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005 Apr;85(2):495-522.
[4] Zhu K, Zhang ML, Liu ST, et al. Ghrelin Attenuates Retinal Neuronal Autophagy and Apoptosis in an Experimental Rat Glaucoma Model. Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6113-6122.
[5] Chen JH, Huang SM, Chen CC, et al. Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells. J Cell Biochem. 2011 Oct;112(10):2931-41.
[6] Sagheb MM, Azarpira N, Mokhtary M. The effect of ghrelin on Kiss-1 and KissR gene transcription and insulin secretion in rat islets of Langerhans and CRI-D2 cell line. Iran J Basic Med Sci. 2017 Jan;20(1):36-40.
[7] Ishii N, Tsubouchi H, Miura A, et al. Ghrelin alleviates paclitaxel-induced peripheral neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions in mice. Eur J Pharmacol. 2018 Jan 15;819:35-42.
[8] Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 2001 Sep;74(3):143-7.