[Search for an endogenous ligand of the orphan G protein-coupled receptor--discovery of apelin, a novel biologically active peptide].

In the search for an endogenous ligand of the human orphan receptor APJ, we have isolated from bovine stomach extracts a novel 36-amino acid peptide, designated apelin. The APJ receptor is one of the G protein-coupled orphan receptors, many of which have been considered to be specific receptors for unidentified hormones and neuropeptides. We recently found the presence of apelin in the adipocytes and vascular walls as well as in the stomach. We examined biological activities of apelin and found that apelin lowered blood pressure in rats and also released cholecystokinin(CCK) from dispersed intestinal endocrine cells. Since apelin is an endogenous ligand for the HIV entry coreceptor APJ, we tested the effect of apelin on the entry of HIV in association with CD4, and found that apelin blocked the entry of HIV-1 and HIV-2.