A Potent Nonpeptide Cholecystokinin Antagonist Selective for Peripheral Tissues Isolated from Aspergillus alliaceus

• Published in: Science (American Association for the Advancement of Science) Vol. 230; no. 4722; pp. 177 - 179
• Main Authors: Raymond S. L. Chang, Lotti, Victor J., Monaghan, Richard L., Birnbaum, Jerome, Stapley, Edward O., Goetz, Michael A., Albers-Schönberg, Georg, Patchett, Arthur A., Liesch, Jerrold M., Hensens, Otto D., Springer, James P.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 11.10.1985; American Association for the Advancement of Science
• Subjects: Agonists; Animals; Aspergillus; Aspergillus - metabolism; Benzodiazepinones - isolation & purification; Benzodiazepinones - pharmacology; Biological and medical sciences; Brain; Chemical Phenomena; Chemistry; Cholecystokinin; Cholecystokinin - antagonists & inhibitors; Cholecystokinin - pharmacology; Cholecystokinin - physiology; Cholecystokinin receptors; Dose-Response Relationship, Drug; Drugs; Gallbladder; Gallbladder - drug effects; General pharmacology; Guinea Pigs; Guinea pigs as laboratory animals; Ileum; Ileum - drug effects; Inhibitory concentration 50; Laboratory animals; Medical sciences; Neuropeptides; Pancreas - drug effects; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Physiological aspects; Rats; Receptors; Receptors, Cell Surface - drug effects; Receptors, Cholecystokinin; Research and development laboratories; Fungi; Stomach; Brain (Vertebrata); Isolation; Antagonist; Cholecystokinin; Thallophyta; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2994227

A new, competitive, nonpeptide cholecystokinin (CCK) antagonist, asperlicin, was isolated from the fungus Aspergillus alliaceus. The compound has 300 to 400 times the affinity for pancreatic, ileal, and gallbladder CCK receptors than proglumide, a standard agent of this class. Moreover, asperlicin is highly selective for peripheral CCK receptors relative to brain CCK and gastrin receptors. Since asperlicin also exhibits long-lasting CCK antagonist activity in vivo, it should provide a valuable tool for investigating the physiological and pharmacological actions of CCK.