Abstract
Growth hormone and insulin like growth factor-1 plays an important role in the regulation of body composition and metabolism. Growth Hormone is released from the pituitary through a specific G-protein coupled receptor (GPCR) called growth hormone secretagogue receptor 1a expressed in the hypothalamus. Ghrelin is a peptide hormone released from the cells in the stomach, which stimulates appetite and food intake in mammals, regulates gut motility, gastric acid secretion, taste sensation, circadian rhythm, learning and memory, oxidative stress, autophagy, glucose metabolism etc. When the release of the endogenous ligand GHSR-1a, i.e., ghrelin is malfunctioned or stopped, external substitutes are administrated to induce the stimulation of growth hormone and appetite. A class of compound known as ghrelin receptor agonists are developed as an external substitute of ghrelin for regulation and stimulation of growth hormone in frailty, for body weight gain, muscle mass gain, prevention of cachexia and for the treatment of chronic fatigue syndromes. Capromorelin [Entyce™ (Aratana Therapeutics, Leawood, KS, USA)] is the only FDA (Food and Drug Administration) approved (May 2016) drug used for stimulating appetite in dogs and was marketed in the fall of 2017. In 2020, USFDA approved Capromorelin [Elura™ (Elanco US Inc.)] for the management of weight loss in chronic kidney disease of cats. This article reviews the discovery of the ghrelin receptor agonist capromorelin, its efficacy, safety, clinical applications and aims to delineate its further scope of use in veterinary practice.
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(adapted from IUPHAR/BPS Guide to PHARMACOLOGY). Ghrelin receptor is a G-protein coupled receptor with seven transmembrane domains. GhSR utilizes distinct G-proteins such as Gα12/13, Gαi/0, Gαq/11 which activates secondary messengers. GHSR can lead to the formation of cyclic AMP (cAMP) or leads to activation of phospholipase C (PLC) that may function through calcium release. This signaling intricate mechanisms often involve rho guanine exchange factors that includes RhoA and associated kinase proteins. β-arrestins also gets activated by GHSR causing attenuation of the downstream signaling by receptor internalization
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The author acknowledges CSIR, India and CSIR-CDRI, Lucknow for providing the facilities. CSIR-CDRI communication number for this manuscript is 10636.
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ND is supported by SERB-NPDF fellowship (PDF/2020/001806).
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MR reviewed the literature and prepared the draft, NG and ND edited the manuscript and prepared the figures, and RG conceived the idea and edited the manuscript. ND and RG contributed equally to the work.
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Rathore, M., Das, N., Ghosh, N. et al. Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine. Vet Res Commun 48, 1–10 (2024). https://doi.org/10.1007/s11259-023-10184-0
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DOI: https://doi.org/10.1007/s11259-023-10184-0