A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus.

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.

[1]  J. Morley,et al.  Minireview. The ascent of cholecystokinin (CCK) - from gut to brain. , 1982, Life sciences.

[2]  S. Snyder,et al.  Distinct cholecystokinin receptors in brain and pancreas. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[3]  L. Moroder,et al.  Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro , 1982, Regulatory Peptides.

[4]  G. Le Fur,et al.  Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. I. In vitro studies. , 1983, Life sciences.

[5]  I. Goldfine,et al.  Characterization of Receptors for Cholecystokinin and Related Peptides in Mouse Cerebral Cortex , 1981, Journal of neurochemistry.

[6]  R. Chang,et al.  Increase in brain 125I-cholecystokinin (CCK) receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions. , 1983, Life sciences.

[7]  R. Chang,et al.  Inactivation of cholecystokinin receptors in rat pancreatic membranes by sulfhydryl reagents: protection by guanosine 5'-triphosphate (GTP) but not N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (dibutyryl cGMP). , 1984, Biochemical pharmacology.

[8]  G. Scatchard,et al.  THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS , 1949 .

[9]  D. Krieger.  Brain peptides: what, where, and why? , 1983, Science.

[10]  C. Braestrup,et al.  Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Holmes,et al.  Cloning of Shiga-like toxin structural genes from a toxin converting phage of Escherichia coli. , 1985, Science.

[12]  R. Jensen,et al.  Cholecystokinin-27-32-amide. A member of a new class of cholecystokinin receptor antagonists. , 1983, The Journal of biological chemistry.

[13]  R. Chang,et al.  Further evidence that substance P partly mediates the action of cholecystokinin octapeptide (CCK-8) on the guinea pig ileum but not gall bladder: Studies with a substance P antagonist , 1984, Neuroscience Letters.