Poria cocos Wolf (P. cocos Wolf) is used to treat chronic gastritis, edema, nephrosis, gastric atony, acute gastroenteric catarrh, dizziness, emesis and vomiting. Triterpenoids are a class of natural compounds produced by P. cocos Wolf that contain acyclic 30-carbon precursors. In this study, we investigated the effect of triterpenoids (PA, Pachymic acid; DA, dehydroeburicoic acid; HA, 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid) on human 5-hydroxytryptamine 3A (5-HT3A) receptor channel activity, which is one of the ligand-gated ion channel families. The two-electrode voltage-clamp technique was used to examine the 5-HT3A mediated current. The inhibitory effect of triterpenoids on 5HT-induced inward current (I5-HT) occurred in a concentration dependent and reversible manner. Furthermore, the half-inhibitory concentrations (IC50) of PA, DA and HA were 3.2 ± 0.2, 5.5 ± 0.6 and 1.4 ± 0.2 μM, respectively. This corresponded to an order of potency for the inhibition of I5-HT in oocytes expressing human 5-HT3A receptor of HA > PA > DA. Finally, inhibition of I5HT by triterpenoids occurred in a non-competitive manner, while inhibition by HA and PA showed more voltage-dependency. Taken together, these results indicate that triterpenoids may regulate the expressed 5-HT3A receptors in Xenopus oocytes. Furthermore, this regulation of the ligand-gated ion channel activity by triterpenoids may be one of the pharmacological actions of P. cocos Wolf. © 2009 Elsevier B.V. All rights reserved.
Poria cocos Wolf; Serotonin type 3A receptor; Triterpenoid; Xenopus oocyte
EMTREE drug terms: 3beta hydroxylanosta 7,9(11),24 trien 21 oic acid; dehydroeburicoic acid; pachymic acid; Poria cocos extract; serotonin 3A receptor; triterpenoid; unclassified drug
EMTREE medical terms: animal cell; article; concentration response; controlled study; drug potency; drug structure; gene expression regulation; IC 50; ion current; nonhuman; oocyte; priority journal; voltage clamp; Xenopus
MeSH: Animals; Dose-Response Relationship, Drug; Female; Humans; Lanosterol; Membrane Potentials; Microinjections; Molecular Structure; Oocytes; Patch-Clamp Techniques; Poria; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; RNA, Complementary; Serotonin; Serotonin Antagonists; Triterpenes; Tropanes; Xenopus laevis
Medline is the source for the MeSH terms of this document.
Chemicals and CAS Registry Numbers: pachymic acid, 29070-92-6;3-hydroxylanosta-7,9(11),24-trien-21-oic acid; HTR3A protein, human; Lanosterol, 79-63-0; RNA, Complementary; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin, 50-67-9; Serotonin Antagonists; Triterpenes; Tropanes; bemesetron, 40796-97-2; dehydroeburiconic acid; pachymic acid, 29070-92-6