Structural Determination of Two Active Compounds That Bind to the Muscarinic M3 Receptor in Beer
Article first published online: 27 FEB 2007
Alcoholism: Clinical and Experimental Research
Volume 31, Issue Supplement s1, pages S9–S14, January 2007
How to Cite
Yamaji, N., Yokoo, Y., Iwashita, T., Nemoto, A., Koike, M., Suwa, Y., Wakimoto, T., Tsuji, K. and Nukaya, H. (2007), Structural Determination of Two Active Compounds That Bind to the Muscarinic M3 Receptor in Beer. Alcoholism: Clinical and Experimental Research, 31: S9–S14. doi: 10.1111/j.1530-0277.2006.00280.x
- Issue published online: 27 FEB 2007
- Article first published online: 27 FEB 2007
- Received for publication August 1, 2005; accepted November 14, 2005.
- Gastrointestinal Motility;
- Hordatine A;
- Muscarinic M3 Receptor
Background: It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M3 receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography. The objective of the present study was to identify the 2 active compounds that bind to the muscarinic M3 receptor in beer.
Methods: Structural analyses of the active compounds were performed by fast atom bombardment mass spectra, 1H-nuclear magnetic resonance (NMR), and 13C-NMR spectroscopy. Active compounds were chemically synthesized from p-coumaric acid and agmatine as starting materials. Binding activity to the muscarinic M3 receptor was used to confirm the activity of the synthetic compounds.
Results: It was identified that 2 active compounds had the same structural characteristics: stereoisomers (cis-isomer and trans-isomer), molecular weight=550 and molecular formula=C28H38N8O4. Trans-isomer (compound B) was identified as the known substance hordatine A, a kind of phytoalexin in barley, and cis-isomer (compound A) was found to be a novel compound (tentatively referred to as aperidine). Both naturally present and chemically synthesized aperidine (compound A) and hordatine A (compound B) were demonstrated to have potent binding activities to the muscarinic M3 receptor.
Conclusions: The 2 active compounds isolated from beer, namely aperidine (compound A) and hordatine A (compound B), have structurally and functionally been identified as active entities of binding to the muscarinic M3 receptor.