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Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry.

Kuwanon G and H, isolated from the methanol extract of Morus bombycis, inhibited specific binding of [125I]gastrin-releasing peptide (GRP) to GRP-preferring receptors in murine Swiss 3T3 fibroblasts with Ki values of 470 and 290 nM, respectively. Kuwanon H was one order of magnitude less potent for inhibiting [125I]bombesin binding to neuromedin B (NMB)-preferring receptors in rat esophagus membranes. This compound 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 physiological and pathological role of GRP.