This discovery relates to acetylcholine, cholinergic signal transduction, bile acid, and methods of treating medical disorders comprising administration of chimeric molecules and/or compositions.
Investigation into the actions of bile acids on gastric chief cells revealed that conjugates of lithocholic acid stimulate pepsinogen secretion by a cholinergic mechanism. Further, the actions of these bile acids on pepsinogen secretion were inhibited by cholinergic antagonists. Also, these bile acids inhibited binding of a muscarinic radioligand to chief cell receptors and stimulated an atropine-sensitive increase in chief cell inositol phosphate production. Researchers concluded that lithocholic acid conjugates bind to muscarinic receptors, thereby stimulating the same cellular signaling pathways as acetylcholine, previously the only known endogenous cholinergic agonists.
The structural similarities between acetylcholine and lithocholic acid indicates a potential molecular basis for interaction with the same receptor, suggesting that chimera of bile acids and cholinergic agents might result in more potent or efficacious agonists, inverse agonists or antagonists for the muscarinic receptor. Additional testing produced findings that support the hypothesis that bile acid - cholinergic agent chimera may be more potent or efficacious muscarinic agonists, inverse agonists or antagonists, depending on structure, than naturally occurring agents.
Reference: Digestive Disease Week 2000 Abstract, Gastroenterology 118: A82, 2000
U.S. Patent #6,624,155
U.S. Patent #6,624,156
Licensing Status: Available for Exclusive Licensing
Licensing Partner to Commercialize this Technology
Mr. Christopher Fasel
Associate Director or Licensing
UAMS BioVentures - TLO
Medical School - Teaching Hospital - Research InstitutionView profile
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