Nicotine-induced catecholamine (CA) secretion and inward ionic currents were 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 (IC50=29 μM). In voltage-clamped chromaffin cells, nicotine (10 μM) evoked an average peak inward current of -146 pA that was inhibited by low concentrations of naloxone (42% at 0.1 μM). The antagonist also inhibited total charge influx associated with nicotinic receptor activation (53% at 0.1 μM). This provides strong evidence that naloxone modulation of nicotine-induced CA secretion does not involve opioid receptors but results from the direct interaction with the nicotinic receptor itself, which might also be the case for other related opioid compounds.
Bibliographical noteFunding Information:
This work has been supported in part by grants SAF96-0169 and 1FD97-0500 from CICYT to V.C.; PRAXIS 2/2.1/SAU/1179/95 from Fundação para a Ciência e Tecnologia (FCT) to L.M.R. and SAF98-0140 from CICYT to C.G.G.
- Catecholamine secretion
- Nicotinic receptor