Naloxone inhibits nicotine-induced receptor current and catecholamine secretion in bovine chromaffin cells

Nicotine-induced catecholamine (CA) secretion and inward ionic currents wer e inhibited by the opioid antagonist naloxone in cultured bovine chromaffin cells. Naloxone inhibited nicotine-induced CA secretion, as detected by an on-line real-time electrochemical technique, in a dose-dependent manner (I C50=29 muM). In voltage-clamped chromaffin cells, nicotine (10 muM) evoked on average peak inward current of -146 pA that was inhibited by low concent rations of naloxone ( 42% at 0.1 muM). The antagonist also inhibited total charge influx associated with nicotinic receptor activation (53% at 0.1 muM ). This provides strong evidence that naloxone modulation of nicotine-induc ed CA secretion does not involve opioid receptors but results from the dire ct interaction with the nicotinic receptor itself, which might also be the case for other related opioid compounds. (C) 2001 Elsevier Science B.V. All rights reserved.