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Orally active anti-hypertensive peptides found based on enteroendocrine cell responses to a dipeptide library
Masaki Sasai1, XingHui Sun1, Chinatsu Okuda1
1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, 611-0011, Japan.
Abstract:
We previously reported that an orally administered dipeptide, Arg-Phe (RF), which causes enteroendocrine cell responses, lowered blood pressure in spontaneously hypertensive rats (SHRs). In this study, we found that Phe-Trp (FW), induced the most potent enteroendocrine cell responses out of total 338 dipeptides. An FW analogue, Phe-Trp-Gly-Lys (FWGK), which was effectively produced by tryptic digestion of bovine serum albumin, decreased blood pressure after oral administration. The minimum effective dose of FWGK (50 μg/kg) was 1/300 of that of RF (15 mg/kg). FWGK stimulated cholecystokinin (CCK) secretion in the enteroendocrine cells and exhibited vasorelaxing and antihypertensive effects via the CCK1 system.
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