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.
Mihara
S
S
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hara
M
M
Nakamura
M
M
Sakurawi
K
K
Tokura
K
K
Fujimoto
M
M
Fukai
T
T
Nomura
T
T
D016475:3T3 Cells; D000818:Animals; D001839:Bombesin / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007457:Iodine Radioisotopes; D000432:Methanol; D051379:Mice; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010944:Plants / Q000737:chemistry*; D051381:Rats; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*
D005419:Flavonoids; D007457:Iodine Radioisotopes; D010455:Peptides; D018004:Receptors, Bombesin; D007334:Insulin-Like Growth Factor I; C095194:kuwanon G; C095195:kuwanon H; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin; D000432:Methanol