[Inhibitory effect of a new proglumide derivative, loxiglumide, on CCK action in isolated rat pancreatic acini].
The effect of a new proglumide derivative, loxiglumide (DL-4-(3,4-dichloro-benzoyl-amino)-5-(N-3-methoxy-propyl-pentylamino+ ++)-5-oxo-pentanic acid; CR 1505), on binding of 125I-CCK-8 and amylase release stimulated by CCK-8 was investigated in isolated rat pancreatic acini. Loxiglumide inhibited CCK-8-stimulated amylase release and binding of 125I-CCK-8 to rat pancreatic acini in a dose-dependent manner. Loxiglumide caused a concentration-dependent rightward shift of the dose-response curve for CCK-8-stimulated amylase release without altering the maximal response. Schild plots showed a slope of 0.82 and pA2 value of 7.05. The inhibitory effect of loxiglumide on amylase release was reversible. Loxiglumide significantly inhibited amylase release in response to CCK-8, caerulein and gastrin-I. However, loxiglumide had no effect on amylase release stimulated by other receptor secretagogues (bombesin, carbamylcholine, secretion and vasoactive intestinal polypeptide) or by agents bypassing receptors (A23187 and TPA). These results indicate that loxiglumide acts as a potent, competitive and specific CCK antagonist on the pancreatic acini.
Fujii
M
M
Otsuki
M
M
Nakamura
T
T
Okabayashi
Y
Y
Tani
S
S
Fujisawa
T
T
Koide
M
M
Baba
S
S
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D005973:Glutamine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000378:metabolism
D005973:Glutamine; C053737:loxiglumide; D002766:Cholecystokinin; D000681:Amylases; D011377:Proglumide; D012844:Sincalide