2015
DOI: 10.1016/j.neuropharm.2015.01.022
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Inside-out neuropharmacology of nicotinic drugs

Abstract: Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable A… Show more

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Cited by 85 publications
(87 citation statements)
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References 126 publications
(417 reference statements)
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“…We have not worked previously with CHOP antibodies. Many commercially available CHOP antibodies fail evaluations for specificity, as discovered by Haataja et al (2008). Haataja et al (2008) recommended verifying that a known inducer of ER stress, such as Tu, does increase the level of nuclear CHOP.…”
Section: Methodsmentioning
confidence: 99%
See 2 more Smart Citations
“…We have not worked previously with CHOP antibodies. Many commercially available CHOP antibodies fail evaluations for specificity, as discovered by Haataja et al (2008). Haataja et al (2008) recommended verifying that a known inducer of ER stress, such as Tu, does increase the level of nuclear CHOP.…”
Section: Methodsmentioning
confidence: 99%
“…Many commercially available CHOP antibodies fail evaluations for specificity, as discovered by Haataja et al (2008). Haataja et al (2008) recommended verifying that a known inducer of ER stress, such as Tu, does increase the level of nuclear CHOP. We therefore performed pilot experiments with a CHOP antibody, Santa Cruz Biotechnology sc-575 (1:250 dilution), also validated by Haataja et al (2008).…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…It is possible that cotinine-induced up-regulation results from a similar mechanism as nicotine, likely acting inside the cell by binding immature subunits to enhance the maturation and stabilization of nAChRs (18,52). This chaperoning process is not unique to nicotine, and can potentially occur with any ligand that readily permeates cell membranes and interacts with intracellular nAChRs.…”
Section: Discussionmentioning
confidence: 99%
“…Nicotine can easily traverse membrane barriers due to its lipophilic nature and activate nicotinic acetylcholine receptors (nAChRs) (Langley 1905, Henderson & Lester 2015. Endogenous agonists such as acetylcholine normally bind nAChRs to regulate downstream cellular and physiological responses; however, exogenous agents like nicotine can compete for the binding sites and exert alternative, and potentially pathological, effects (Albuquerque et al 2009).…”
Section: Pharmacology Of Nicotinementioning
confidence: 99%