Anti-5-hydroxytryptamine3 effect of galanolactone, diterpenoid isolated from ginger.
It has been reported that an acetone extract of ginger and its fractions have anti-5-HT (5-hydroxytryptamine; serotonin) effects. In the present study, guinea pig ileum, rat stomach fundus and rabbit aortic strips are used in order to determine the constituents of fraction 2 which are responsible for anti-5-HT effect and to examine their pharmacological properties. The analysis of fraction 2-3 indicated that galanolactone, a diterpenoid, is one of the active constituents. In guinea pig ileum, galanolactone inhibited contractile responses to 5-HT with a pIC50 value 4.93. pIC50 value of galanolactone against the response to 2-methyl-5-HT, a selective 5-HT3 agonist, in the presence of methysergide at 1 x 10(-5) M was 5.10. pIC50 values of ICS 205-930, a selective 5-HT3 antagonist, were 5.30 and 7.49, respectively. The concentration-response curve of 5-HT was shown as a biphasic curve and galanolactone caused a selective shift to the right of the second phase. In the same preparations, the pIC50 value of galanolactone and ICS 205-930 against the response to carbamylcholine (CCh) was 4.45 and 4.46. The inhibitory effect of galanolactone on the 5-HT response in the stomach fundus and aortic strips was less than that in the ileum. In addition, in the thoracic aorta precontracted with 50 mM K+, the relaxing effect of galanolactone was about 1/10 of that of papaverine. These results suggest that the anti-5-HT effect of galanolactone, a diterpenoid isolated from ginger, is related to antagonism of 5-HT3 receptors.
Huang
Q R
QR
Kyoto Pharmaceutical University, Japan.
Iwamoto
M
M
Aoki
S
S
Tanaka
N
N
Tajima
K
K
Yamahara
J
J
Takaishi
Y
Y
Yoshida
M
M
Tomimatsu
T
T
Tamai
Y
Y
D000818:Animals; D003212:Condiments / Q000032:analysis*; D004224:Diterpenes / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*
D004224:Diterpenes; D012702:Serotonin Antagonists; C069419:galanolactone