Asperlicin: A unique nonpeptide cholecystokinin antagonist

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 < 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 < 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.