Isolation from beer and structural determination of a potent stimulant of gastrin release.
Beer was subjected to five successive chromatographic procedures to isolate the gastrin release-inducing activity, guided by bioassay of the fractions in anaesthetized Donryu rats. The procedures were: (1) hydrophobic interaction chromatography (aqueous effluent with an HP20 column); (2) weak cation-exchange chromatography (1 M acetic acid eluate with a CM Sephadex C-25 column); (3) gel filtration (methanol eluate with a Sephadex LH-20 column); (4) same as (2); (5) high-performance liquid chromatography (YMC-Pack ODS-AM with 7% acetonitrile-0.01 M HCl). The active component finally isolated had a specific activity approximately 10000 times higher than that of beer. It was identified by means of mass, 1H- and 13C-nuclear magnetic resonance spectral analyses as N-methyltyramine (NMT). The dose of NMT giving maximal gastrin-releasing activity was 25 microg/kg, and the 50% effective dose was approximately 10 microg/kg on oral administration to rats. NMT was isolated and identified as a gastrin release inducer in beer. Its concentration in beer is sufficient to account for most of the activity of beer.
Yokoo
Y
Y
Technical Development Department, Suntory Limited, Mishima-Gun, Osaka, Japan.
Kohda
H
H
Kusumoto
A
A
Naoki
H
H
Matsumoto
N
N
Amachi
T
T
Suwa
Y
Y
Fukazawa
H
H
Ishida
H
H
Tsuji
K
K
Nukaya
H
H
D000316:Adrenergic alpha-Agonists / Q000302:isolation & purification*; D000818:Animals; D001515:Beer / Q000032:analysis*; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D051381:Rats; D014439:Tyramine / Q000031:analogs & derivatives* / Q000302:isolation & purification
D000316:Adrenergic alpha-Agonists; D005755:Gastrins; C036244:methyl-4-tyramine; D014439:Tyramine