Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells.
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 microM) concentration-dependently stimulated catecholamine secretion and (45)Ca(2+) influx. Its stimulatory effect of nobiletin on catecholamine secretion was abolished by deprivation of extracellular Ca(2+) and partially inhibited by specific inhibitors of voltage-dependent Ca(2+) channels and Na(+)/Ca(2+) exchangers. On the other hand, nobiletin suppressed catecholamine secretion and (22)Na(+) and (45)Ca(2+) influx induced by acetylcholine, an agonist of nicotinic acetylcholine receptors, in a concentration-dependent manner. It also inhibited catecholamine secretion, (22)Na(+) influx and/or (45)Ca(2+) 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 alpha3beta4 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 Ca(2+) channels or Na(+)/Ca(2+) exchangers, whereas it inhibits catecholamine secretion induced by acetylcholine through the suppression of Na(+) influx and Ca(2+) influx in cultured bovine adrenal medullary cells.
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu, Japan.
Han
H
Zhang
Yumiko
Y
Toyohira
Susumu
S
Ueno
Yuko
Y
Shinohara
Hideaki
H
Itoh
Yumi
Y
Furuno
Tohru
T
Yamakuni
Masato
M
Tsutsui
Kojiro
K
Takahashi
Nobuyuki
N
Yanagihara
D000313:Adrenal Medulla / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D002957:Citrus / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000494:pharmacology*; D009865:Oocytes; D010936:Plant Extracts / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D014981:Xenopus
D000975:Antioxidants; D015220:Calcium Channels; D002395:Catecholamines; D047309:Flavones; D010936:Plant Extracts; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; C008661:nobiletin; D002118:Calcium