title: Asperlicin: a unique nonpeptide cholecystokinin antagonist.
abstract: The lack of a potent and specific cholecystokinin (CCK) receptor antagonist has greatly hampered studies of the role of CCK in controlling pancreatic growth, enzyme release, pancreatitis, and pancreatic carcinoma. Asperlicin, a newly described, CCK antagonist, has been shown to be a potent, competitive inhibitor of CCK-induced gallbladder and ileal muscle contraction. In this study, the effects of asperlicin on CCK- and carbachol-stimulated pancreatic enzyme release from dispersed guinea pig acini were investigated. Cholecystokinin caused a dose-dependent release of amylase and lipase. Half-maximal release of amylase (17.9% +/- 2.1%, mean +/- SEM, percent of total content) and lipase (27.3% +/- 2.1%) was seen with CCK 10(-11) mmol/L) both p less than 0.01). Asperlicin (10(-11) to 10(-4) mmol/L) caused a substantial inhibition (10(-11) mmol/L) of CCK-induced amylase release with a 50% maximal effective inhibitory dose of 10(-9) mmol/L (p less than 0.01) and maximum inhibition at 10(-6) mmol/L. Asperlicin was approximately 1000-fold more potent than proglumide (a previously described CCK receptor antagonist) which had a 50% effective inhibitory dose of 10(-6) mmol/L) and a maximal effect at 10(-4) mmol/L. Asperlicin (10(-10) to 10(-4) mmol/L) failed to alter carbachol-induced amylase release. Asperlicin is a new, potent CCK antagonist for pancreatic CCK receptors and should prove useful as an investigational tool. Such receptor antagonists may have therapeutic potential.
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D008049:Lipase / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D011377:Proglumide / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects
chemical_list: D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002217:Carbachol; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D011377:Proglumide; C046367:asperlicin