Naloxone inhibits nicotine-induced receptor current and catecholamine secretion in bovine chromaffin cells.
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 (IC(50)=29 microM). In voltage-clamped chromaffin cells, nicotine (10 microM) evoked an average peak inward current of -146 pA that was inhibited by low concentrations of naloxone (42% at 0.1 microM). The antagonist also inhibited total charge influx associated with nicotinic receptor activation (53% at 0.1 microM). 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.
Tomé
A R
AR
Department of Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Izaguirre
V
V
Rosário
L M
LM
Ceña
V
V
González-García
C
C
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000502:physiology
D002395:Catecholamines; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D018847:Opioid Peptides; D011978:Receptors, Nicotinic; D009270:Naloxone; D009538:Nicotine