Sensitivity of neuronal nicotinic acetylcholine receptors to the opiate antagonists naltrexone and naloxone: receptor blockade and up-regulation.
In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent up-regulation of functional alpha7 nAChRs that was detected after removal of the drug. These results indicate that naltrexone could be used as a smoking cessation aid.
Almeida
Luis E F
LE
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Pereira
Edna F R
EF
Camara
Adriana L
AL
Maelicke
Alfred
A
Albuquerque
Edson X
EX
D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D016540:Smoking Cessation / Q000379:methods; D013329:Structure-Activity Relationship; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D009292:Narcotic Antagonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D009270:Naloxone; D009271:Naltrexone; D009538:Nicotine