title: Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.
abstract: Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Horisita
authors.affiliation: Shared-Use Research Center, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Satoh
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshinaga
authors.affiliation: Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of The Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. yanagin@med.uoeh-u.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D018733:Nicotinic Antagonists / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves; D011978:Receptors, Nicotinic / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels; D002395:Catecholamines; D005419:Flavonoids; D006027:Glycosides; C538782:Ikarisoside A; D018733:Nicotinic Antagonists; D010936:Plant Extracts; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D000109:Acetylcholine
keywords: Adrenal medulla; Catecholamine secretion; Epimedium; Flavonoids; Ikarisoside A; Nicotinic acetylcholine receptor