NONPEPTIDE BOMBESIN RECEPTOR ANTAGONISTS, KUWANON-G AND KUWANON-H, ISOLATED FROM MULBERRY

Kuwanon G and H, isolated from the methanol extract of Morus bombycis, inhibited specific binding of [I-125]gastrin-releasing peptide (GRP) to GRP-preferring receptors in murine Swiss 3T3 fibroblasts with K-i v alues of 470 and 290 nM, respectively. Kuwanon H was one order of magn itude less potent for inhibiting [I-125]bombesin binding to neuromedin B (NMB)-preferring receptors in rat esophagus membranes. This compoun d antagonized bombesin-induced increases in the cytosolic free calcium concentration and GRP-induced DNA synthesis in Swiss 3T3 cells. Thus, kuwanon H, and possibly kuwanon G also, are specific antagonists for the GRP-preferring receptor and can be useful for studying the physiol ogical and pathological role of GRP. (C) 1995 Academic Press. Inc.