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

Han Zhang, Yumiko Toyohira, Susumu Ueno, Yuko Shinohara, Hideaki Itoh, Yumi Furuno, Tohru Yamakuni, Masato Tsutsui, Kojiro Takahashi, Nobuyuki Yanagihara

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 M) 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 andor 45Ca2+ influx induced by veratridine, an activator of voltage-dependent Na+ channels, and 56 mM K+, an activator of voltage-dependent Ca 2+ channels. In Xenopus oocytes expressing 34 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.

Original languageEnglish
Pages (from-to)1030-1038
Number of pages9
JournalJournal of Neurochemistry
Volume114
Issue number4
DOIs
Publication statusPublished - 2010 Aug

Keywords

  • adrenal medulla
  • catecholamine secretion
  • dual effects
  • ion influx
  • nobiletin
  • voltage-dependent Ca channels

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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