Isolation of stimulants of gastrointestinal motility in beer.
BACKGROUND
Among various alcoholic beverages, it has reported that beer has a potent activity to stimulate gastric emptying. Our previous studies showed that beer congener stimulated gastrointestinal motility by directly stimulating muscarinic M3 receptor, present in smooth muscles of the gastrointestinal tract. However, active components that account for the action have yet to be identified. We attempted to isolate the stimulant(s) of gastrointestinal motility in beer.


METHODS
Beer congener was prepared from beer and used to separate and purify active components by a series of liquid chromatography using affinity to muscarinic M3 receptor as an index. Gastrointestinal motility-stimulating activity was evaluated using a test for activity that causes contraction of longitudinal muscles in guinea pig ileum and a test for gastric emptying activity in mice.


RESULTS
The active components (compounds A and B) were purified and isolated from beer by four liquid chromatography steps. The IC50 values of two active isolates to muscarinic M3 receptor were 0.65 x 10 g/ml and 2.30 x 10 g/ml, respectively. The concentrations of compounds A and B contained in beer were sufficient to explain most of the muscarinic M3 receptor binding activity of beer. The active fraction that contained both compounds A and B (which was 10 times as active as beer congener in muscarinic M3 receptor binding activity) dose-dependently contracted the longitudinal muscles of guinea pig ileum with an activity that was 20 times as potent as that of beer congener. The same active fraction significantly stimulated gastric emptying in mice with an activity 20 times as potent as that of beer congener.


CONCLUSIONS
Two active components (compounds A and B) were isolated as gastrointestinal motility stimulants (muscarinic M3 agonists) in beer. These results suggest that the two isolated active components are the active entities of the gastrointestinal motility-stimulating effect of beer.
Yokoo
Yoshiaki
Y
Technical Development Department, Suntory Limited, Osaka, Japan. yoshiaki_yokoo@suntory.co.jp
Fujii
Wataru
W
Hori
Hisako
H
Nagao
Koji
K
Suwa
Yoshihide
Y
Taniyama
Kohtaro
K
Tsuji
Kuniro
K
Yoshida
Toshiyuki
T
Nukaya
Haruo
H
D000818:Animals; D001515:Beer / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000302:isolation & purification / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D043587:Receptor, Muscarinic M3 / Q000502:physiology
D005731:Ganglionic Stimulants; D043587:Receptor, Muscarinic M3