The role of endogenous gastrin in the development of enterochromaffin-like cell carcinoid tumors in Mastomys natalensis: a study with the specific gastrin receptor antagonist AG-041R.
We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach.
Chiba
T
T
Department of Internal Medicine, Postgraduate School of Medicine, Kyoto University, Japan.
Kinoshita
Y
Y
Sawada
M
M
Kishi
K
K
Baba
A
A
Hoshino
E
E
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002276:Carcinoid Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019861:Enterochromaffin-like Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D064747:Lansoprazole; D008297:Male; D009115:Muridae; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C109755:AG-041R; D001570:Benzodiazepinones; D005755:Gastrins; D007211:Indoles; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D064747:Lansoprazole; C058121:L 365260; D009853:Omeprazole; D013936:Thymidine