title: Effects of triterpenoids from Poria cocos Wolf on the serotonin type 3A receptor-mediated ion current in Xenopus oocytes.
abstract: 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, 3beta-hydroxylanosta-7,9(11),24-trien-21-oic acid) on human 5-hydroxytryptamine 3A (5-HT(3A)) 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 (I(5-HT)) occurred in a concentration dependent and reversible manner. Furthermore, the half-inhibitory concentrations (IC(50)) of PA, DA and HA were 3.2+/-0.2, 5.5+/-0.6 and 1.4+/-0.2 microM, respectively. This corresponded to an order of potency for the inhibition of I(5-HT) in oocytes expressing human 5-HT(3A) receptor of HA>PA>DA. Finally, inhibition of I(5HT) 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-HT(3A) 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.
authors.affiliation: Department of Physiology, College of Oriental Medicine, Kyung-Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jung-Kyu
authors.initials: JK
authors.lastname: Shin
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Jeong
authors.forename: Yangseok
authors.initials: Y
authors.lastname: Kim
authors.forename: Minkyu
authors.initials: M
authors.lastname: Shin
authors.forename: Moochang
authors.initials: M
authors.lastname: Hong
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Seo
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D055441:Poria / Q000737:chemistry*; D018075:RNA, Complementary / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: C544691:3-hydroxylanosta-7,9(11),24-trien-21-oic acid; C509409:HTR3A protein, human; D018075:RNA, Complementary; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014315:Triterpenes; D014326:Tropanes; C492580:dehydroeburiconic acid; D007810:Lanosterol; D012701:Serotonin; C042253:bemesetron; C102487:pachymic acid