Ghrelin GPCR Assays

Please Click Here to Browse the Assay List

Background of Ghrelin Receptors

Ghrelin is the endogenous ligand of the ghrelin G protein-coupled receptor. Ghrelin acts on the somatotrophs and hypothalamus, promoting the growth hormone-releasing hormone release. Ghrelin also modulates the cardiovascular system, acting as the vasodilator in vivo and in vitro. In addition, ghrelin is involved in enhancing gastric acid secretion and motility, playing an important role in the acute and long-term modulation of appetite and energy homeostasis. It has been indicated that ghrelin enhanced food intake, weight gain as well as hepatic lipogenesis and reduced the utilization and activation of adipose tissue. Ghrelin levels in people with obesity are modest, whereas they are substantially greater in normal-weight individuals. Ghrelin may also control many physiological processes, including attention and memory.

Fig.1 Multiple signaling pathways of the ghrelin receptor. (Sivertsen, 2013)

Distribution and Function of Ghrelin Receptors

Ghrelin receptors are principally located in the gastrointestinal tract, vasculature, hypothalamus, hippocampus, somatotrophs, and so on. Discovering the ghrelin receptor agonists or antagonists may provide us an opportunity for the treatment of human atherosclerosis, familial short stature, chronic heart failure, or the management of obesity.

Subtypes and Mechanisms of Ghrelin Receptors

The family of ghrelin receptors only has one subtype of receptor. Ghrelin receptor signal transduction is mediated by G_q/G₁₁, G_i/G_o, and G₁₂/G₁₃ proteins.

Receptor	Gene	Mechanism	Agonists	Antagonists
Ghrelin receptor	GHSR	Ghrelin receptor binds to galanin and G_q/G₁₁ protein to stimulate phospholipase C Ghrelin receptor also couples G_i/G_o protein, G₁₂/G₁₃ protein Ghrelin receptor activates the adaptor-related protein complex and β-arrestin	ghrelin ibutamoren GHRP-6 SM-130,686 wFw-Isn-NH₂ macimorelin	BIM 28163 PF-05190457 YIL781 GSK1614343 JMV3008 Abbott 14c

Assay List of Ghrelin Receptor

Creative Biolabs can provide a range of assays of ghrelin receptor. You can choose the assay in the list or contact us for more information:

GHSR

Assay No.	Assay Name	Host Cell	Assay Type
Calcium Flux Assay
S01YF-0722-KX112	Magic™ Human GHSR In Vitro Calcium Assay & Binding Assay, HEK293	HEK293	Calcium Assay; Binding Assay
IP1 Assay
S01YF-1122-KX486	Magic™ Human GHSR In Vitro IP1 Assay	CHO-K1	IP1 Assay

Published Data

Paper Title	LEAP2 is an endogenous antagonist of the ghrelin receptor
Journal	Cell metabolism
Published	2018
Abstract	Ghrelin is a hormone-stimulating appetite and growth hormone (GH) secretion, which is secreted by the stomach. It was found to be a ligand for the growth hormone secretagogue receptor (GHSR). It exerts as a regulator for GH secretion to protect against starvation-induced hypoglycemia. The study reported a newly discovered endogenous antagonist of GHSR, liver-expressed antimicrobial peptide 2 (LEAP2). LEAP2 is produced in the liver and small intestine and is suppressed by fasting. The study used in vitro and in vivo experiments to investigate the modulating function of LEAP2 on ghrelin in response to physiological conditions. Using function-blocking antibodies to inhibit LEAP2, which enhanced ghrelin action.
Result	They utilized a mouse model of vertical sleeve gastrectomy (VSG) that investigated the expression level of Leap2 increased 52-fold. The test of the activity of LEAP2 against 168 known human GPCRs showed that LEAP2 fully inhibited the activity of GHSR. Ghrelin activated GHSR with an EC₅₀ of 7.1 nM. LEAP2 fully inhibited ghrelin-induced GHSR activation with an IC₅₀ of 6.0 nM. The study has demonstrated that LEAP2 is a noncompetitive antagonist of GHSR, likely modulating the receptor through binding to an allosteric site. They transfected COS7 cells with GHSR and then evaluated ligand binding to these cells using Alexa-647-labeled LEAP2 peptide. The result showed that LEAP2 was bound to GHSR-expressing cells. The study also detected the Leap2 expression in the gastrointestinal tracts by quantitative PCR. The results of in vivo experiments indicated that LEAP2 blocked ghrelin-induced food intake in mice. The study has indicated that the LEAP2 completely inhibited GHSR activation by ghrelin and blocked the major effects of ghrelin in vivo including food intake, GH release, and maintenance of viable glucose levels during chronic caloric restriction. They utilized the neutralizing antibodies to block endogenous LEAP2 function, which enhanced ghrelin action in vivo. Fig.2 LEAP2 is a VSG-regulated peptide that antagonizes the ghrelin receptor. (Ge, 2018)

References

Sivertsen, B.; et al. Functionally biased signaling properties of 7TM receptors–opportunities for drug development for the ghrelin receptor. British Journal of Pharmacology. 2013, 170(7): 1349-1362.a
Ge, X.; et al. LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell metabolism. 2018, 27(2): 461-469.

Note: All of our products are for Research Use Only (RUO). NOT intended for diagnostic, therapeutic or clinical use. We DO NOT offer patients any direct products or services. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.