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

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. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.