Physiological and Biochemical Studies on apelin, a novel gastrointestinal hormone from stomach

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The principal aim of this proposal is to study physiological and biochemical characterization of apelin, a novel gastrointestinal hormone isolated from the stomach. Toward this goal, a specific immunoassay for apelin has been developed, and using this assay, we found that apelin is distributed in a wide variety of tissues including the spleen, liver, mammary gland, pancreas, kidney, spinal cord, lung, stomach, brain, intestine, and heart. We also determined the molecular forms of apelin in these tissues. In the lung, kidney, intestine, and brain, a major peak of apelin was observed at a position almost identical to that of apelin-17, while, in the spleen, a major peak was detected at a position corresponding to that of apelin-36. The liver extract seemed to contain two major peptides similar to apelin-13 and apelin-17. We also studied the location of apelin in rat tissues using immunohistochemical techniques. Apelin was present in the endothelia of the small arteries of the spleen, lung, intestine, kidney, heart, pancreas, liver, and gastrointestinal tract. Apelin was also found in the white adipose tissues and the stomach wall. 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. We also found that apelin is present in milk, thus, the peptide may have a role as an exogenous CCK-releasing factor. Since apelin is a ligand for the HIV coreceptor APJ, we tested the effect of apelin on HIV infection, and found that apelin blocked the entry of HIV-1 and HIV-2. Apelin-36 more effectively blocked HIV infection than apelin-12 or apelin-13. We also found that the administration of apelin suppresses cytokine production by mouse spleen cells. These studies support the speculation that apelin may be involved in the modulation of immune responses.