(D-Arg¹,D-Phe⁵,D-Trp⁷·⁹,Leu¹¹)-Substance P
Supplier: BACHEM AMERICAS INC
Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary through a G protein-coupled receptor (GHS-R). Recently, ghrelin ("ghre" is the Proto-Indo-European root of the word "grow") has been identified as an endogenous ligand for GHS-R. These peptides consist of 28 amino acids with an octanoyl-residue at Ser³, which is essential for expressing activity. Ghrelin stimulates GH release from rat primary culture pituitary cells in a dose-dependent manner and induces an increase in intracellular Ca²⁺ in GHS-R-expressing cells with an EC₅₀ value of 2.5 nM. Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin. In future, ghrelin might be used in the treatment of aging patients as well as in patients with idiopathic GH deficiency, obesity, osteoporosis or cardiovascular diseases.
(D-Arg¹,D-Phe⁵,D-Trp⁷·⁹,Leu¹¹)-Substance P initially described as a low potency ghrelin receptor antagonist has surprisingly been found to be a full inverse agonist (EC₅₀ = 5.2 nM). In COS-7 cells transiently transfected with the ghrelin receptor the substance P analog rPKPfQwFwLL decreased the constitutive signaling down to levels observed in untransfected cells. Assuming that constitutive signaling of the ghrelin receptor is of physiological relevance in the regulation of appetite control, inverse agonists of the ghrelin receptor could be interesting for the treatment of obesity. So, Asakawa et al. found that peripherally administered H-6395 decreased food intake in lean mice, in mice with diet induced obesity, and in ob/ob obese mice.
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