title: The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.
abstract: The inhibitory effects of CR-1409, a new glutaramic acid derivative developed as a cholecystokinin (CCK) receptor antagonist, on caerulein-stimulated amylase secretion and on intracellular Ca2+ ([Ca2+]i) mobilization were studied in isolated rat pancreatic acini. Pancreatic acini were prepared by collagenase digestion method and loaded with 1 microM fura-2/AM for measurement of the intracellular free Ca2+ concentration. Amylase release was examined by a perifusion method. Stimulation with 10(-10) M caerulein, 10(-5) M carbachol, or 10(-8) M gastrin-releasing peptide (GRP) led to biphasic amylase release and increase in [Ca2+]i. CR-1409 at 1 and 5 microM inhibited, by 50 and 84%, respectively, the amylase secretion and increase in [Ca2+]i induced by 10(-10) M caerulein, and 25 microM CR-1409 completely inhibited both amylase secretion and increase in [Ca2+]i induced by caerulein. However, 25 microM CR-1409 did not inhibit unstimulated secretion of amylase or the secretions induced by carbachol and GRP, which are also mediated by changes in intracellular Ca2+. We conclude that CR-1409 acts as a specific inhibitor of the CCK receptor in the pancreas, and is useful in studies on the involvement of the release and action of CCK in vitro.
authors: Sanshinkai Hara Hospital, Fukuoka, Japan.
authors: H
authors: H
authors: Shinozaki
authors: A
authors: A
authors: Funakoshi
authors: H
authors: H
authors: Wakasugi
authors: M
authors: M
authors: Abe
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D019886:Gastrin-Releasing Peptide; D005973:Glutamine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence
chemical_list: D001572:Benzofurans; D005456:Fluorescent Dyes; D010455:Peptides; D005973:Glutamine; D019886:Gastrin-Releasing Peptide; D002108:Ceruletide; D002217:Carbachol; D000681:Amylases; D011377:Proglumide; C048181:lorglumide; D002118:Calcium; D016257:Fura-2