Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells

Authors: Zhang, Han¹; Toyohira, Yumiko¹; Ueno, Susumu¹; Shinohara, Yuko²; Itoh, Hideaki¹; Furuno, Yumi¹; Yamakuni, Tohru³; Tsutsui, Masato⁴; Takahashi, Kojiro⁵; Yanagihara, Nobuyuki¹

Source: Journal of Neurochemistry, Volume 114, Number 4, August 2010 , pp. 1030-1038(9)

Publisher: Wiley-Blackwell

Abstract:

J. Neurochem. (2010) 114, 1030-1038. Abstract

Nobiletin, a compound of polymethoxy flavones found in citrus fruits, possesses a wide range of pharmacological activities. Here we report the effects of nobiletin on catecholamine secretion in cultured bovine adrenal medullary cells. Nobiletin (1.0-100 μM) concentration-dependently stimulated catecholamine secretion and ⁴⁵Ca²⁺ influx. Its stimulatory effect of nobiletin on catecholamine secretion was abolished by deprivation of extracellular Ca²⁺ and partially inhibited by specific inhibitors of voltage-dependent Ca²⁺ channels and Na⁺/Ca²⁺ exchangers. On the other hand, nobiletin suppressed catecholamine secretion and ²²Na⁺ and ⁴⁵Ca²⁺ influx induced by acetylcholine, an agonist of nicotinic acetylcholine receptors, in a concentration-dependent manner. It also inhibited catecholamine secretion, ²²Na⁺ influx and/or ⁴⁵Ca²⁺ influx induced by veratridine, an activator of voltage-dependent Na⁺ channels, and 56 mM K⁺, an activator of voltage-dependent Ca²⁺ channels. In Xenopus oocytes expressing α3β4 neuronal acetylcholine receptors, nobiletin directly inhibited the current evoked by acetylcholine in a concentration-dependent manner similar to that observed in catecholamine secretion. The present findings suggest that nobiletin, by itself, stimulates catecholamine secretion via activation of voltage-dependent Ca²⁺ channels or Na⁺/Ca²⁺ exchangers, whereas it inhibits catecholamine secretion induced by acetylcholine through the suppression of Na⁺ influx and Ca²⁺ influx in cultured bovine adrenal medullary cells.

Keywords: adrenal medulla; catecholamine secretion; dual effects; ion influx; nobiletin; voltage-dependent Ca2+ channels

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1471-4159.2010.06840.x

Affiliations: 1: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu, Japan 2: Pharmaceuticals Research Laboratory, Corporate Research & Development, Ube Industries Ltd., Kogushi, Ube, Japan 3: Department of Pharmaceutical Molecular Physiology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan 4: Department of Pharmacology, Faculty of Medicine, University of The Ryukyus, Nishihara, Okinawa, Japan 5: Department of Hospital Pharmacy, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan

Publication date: 2010-08-01

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• In this Subject: Anatomy & Physiology
• By this author: Zhang, Han ;  Toyohira, Yumiko ;  Ueno, Susumu ;  Shinohara, Yuko ;  Itoh, Hideaki ;  Furuno, Yumi ;  Yamakuni, Tohru ;  Tsutsui, Masato ;  Takahashi, Kojiro ;  Yanagihara, Nobuyuki

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