Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine

@article{Buccafusco2007DisconnectionBA,
  title={Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine},
  author={Jerry J. Buccafusco and Laura C Shuster and Alvin V. Terry},
  journal={Neuroscience Letters},
  year={2007},
  volume={413},
  pages={68-71}
}
Cotinine is the major metabolite of nicotine in humans, and the substance greatly outlasts the presence of nicotine in the body. Recently, cotinine has been shown to exert pharmacological properties of its own that include potential cognition enhancement, anti-psychotic activity, and cytoprotection. Since the metabolite is generally less potent than nicotine in vivo, we considered whether part of cotinine's efficacy could be related to a reduced ability to desensitize nicotinic receptors as… Expand
Desensitization of Nicotinic Acetylcholine Receptors as a Strategy for Drug Development
TLDR
The effectiveness of these four compounds in the task was linearly related to their effectiveness in producing desensitization of the pressor response to ganglionic stimulation evoked by a nAChR agonist in rats. Expand
Cotinine Selectively Activates a Subpopulation of α3/α6β2* Nicotinic Receptors in Monkey Striatum
TLDR
The results unexpectedly showed that nicotine evokes dopamine release from two α3/α6β2* nAChR populations, one of which was sensitive to cotinine and the other was not, and this cotinin-insensitive subtype was preferentially lost with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal damage. Expand
Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions
  • Xiaoying Tan, K. Vrana, Zheng-Ming Ding
  • Medicine
  • Frontiers in Behavioral Neuroscience
  • 2021
TLDR
Findings implicating cotinine as a neuroactive metabolite of nicotine and available evidence regarding potential mechanisms underlying its effects are discussed, providing a mixed picture with a lack of consensus. Expand
Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats
TLDR
The results suggest that some non-nicotine tobacco constituents may enhance or reduce nicotine's reinforcing properties, and depending upon the appropriate dose, some of these compounds may also serve as potential smoking cessation agents. Expand
A reversible model of the cognitive impairment associated with schizophrenia in monkeys: potential therapeutic effects of two nicotinic acetylcholine receptor agonists.
TLDR
The DMTS task impairment induced by ketamine was capable of being completely reversed by two compounds that are known to improve working memory and cognition, and the best dose of GTS-21 completely reversed the ketamine-induced task deficits. Expand
The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.
TLDR
The results suggest that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine, may increase the motivation for nicotine and thus facilitate smoking behaviour. Expand
Understanding the Role α7 Nicotinic Receptors Play in Dopamine Efflux in Nucleus Accumbens
TLDR
A circuit modeling approach revealed two potential mechanisms for the drop in accumbal dopamine efflux evoked by the selective α7 partial agonist TC-7020, and offered a rationale for the further investigation of α7 NNR agonists as therapy for diseases associated with enhanced mesolimbic dopaminergic tone, such as schizophrenia and addiction. Expand
Cotinine impacts sensory processing in DBA/2 mice through changes in the conditioning amplitude
TLDR
The data suggest that cotinine modulates the conditioning amplitude in the sensory inhibition paradigm through the α4β2 nicotinic receptor and possibly also through the β-bungarotoxin receptor, as well, however the data do not suggest thatcotinine is a potential therapeutic for the treatment of sensory inhibition deficits in schizophrenia. Expand
Cigarette smoke, nicotine and cotinine protect against 6-hydroxydopamine-induced toxicity in SH-SY5Y cells.
TLDR
The combined results support the idea that nicotine is one of the components in cigarette smoke that has a protective effect against neurotoxic insults and suggest that nicotine may be of potential therapeutic value for Parkinson's disease. Expand
The Effects of Tobacco Smoke and Nicotine on Cognition and the Brain
TLDR
The reviewed evidence suggests caution with the use of medicinal nicotine in pregnant mothers and older adults at risk for certain neurological disease, and the assessment of cognition-related genotypes to better understand the role of interactions between smoking/nicotine and variation in genotype in determining susceptibility to the neurotoxic effects of smoking and the putative beneficial effects of medicinal Nicotine. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 17 REFERENCES
Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition.
TLDR
Based on its relative safety in man, cotinine should prove useful in the treatment of diseases of impaired cognition and behavior without exhibiting the toxicity usually attributed to nicotine. Expand
Nanomolar concentrations of nicotine increase the release of [3H]dopamine from rat striatal synaptosomes
  • P. Rowell
  • Medicine, Biology
  • Neuroscience Letters
  • 1995
TLDR
In this study, an in vitro superfusion system was used to measure the nicotine-evoked release of [3H]dopamine (DA) from rat striatal synaptosomes and it is suggested that the gradual DA release in response to low concentrations of nicotine occurs as a result of either open channel properties of the desensitized receptor or an equilibrium between the high-affinity Desensitized and active states of the nAChRs. Expand
Relationship between the increased cell surface α7 nicotinic receptor expression and neuroprotection induced by several nicotinic receptor agonists
TLDR
The induced upregulation of the α7 subtype of nicotinic receptors during chronic exposure to nicotine may be responsible for the drug's neuroprotective action. Expand
Long-lasting cognitive improvement with nicotinic receptor agonists: mechanisms of pharmacokinetic-pharmacodynamic discordance.
TLDR
Some of the cellular effects of nAChR agonists overlap with the known cellular mechanisms of LTP, including long-lasting increases in intracellular concentrations of Ca2+, activation of second-messenger systems and transcription factors, elevated levels of gene products and enhanced neurotransmitter release. Expand
Safety of Cotinine in Humans: Physiologic, Subjective, and Cognitive Effects
TLDR
This study demonstrates that short-term administration of cotinine to humans at levels as high as 10 times that attained from cigarette smoking is safe with no observable acute or withdrawal effects from cotinines in this setting. Expand
Pharmacological comparison of transient and persistent [3H]dopamine release from mouse striatal synaptosomes and response to chronic L-nicotine treatment.
TLDR
The results are consistent with both phases being mediated by a single type of receptor and inactivation of a portion of the receptors rather than a reversible desensitization is discussed. Expand
Activation and inhibition of the human α7 nicotinic acetylcholine receptor by agonists
TLDR
Even a very weak agonist could appear to be a potent and effective inhibitor through receptor desensitization, at least in part. Expand
Cotinine binding to nicotinic acetylcholine receptors in bovine chromaffin cell and rat brain membranes.
  • P. Vainio, R. Tuominen
  • Chemistry, Medicine
  • Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
  • 2001
TLDR
The results demonstrate that 100 pM to 1 nM [3H]epibatidine labels mostly neuronal heteropentameric nicotinic receptors in bovine chromaffin cell membranes, and that cotinine is a low-affinity Nicotinic ligand both in the adrenal chromaff in cell and in the brain receptors. Expand
Neuronal nicotinic receptor subtypes: defining therapeutic targets.
TLDR
The central actions of nicotine have been examined in earnest for potential therapeutic applications, and the muscarinic and nicotinic cholinergic systems have been relegated mainly to the treatment of gastrointestinal disorders and glaucoma. Expand
Brain Uptake Kinetics of Nicotine and Cotinine after Chronic Nicotine Exposure
TLDR
This is the first report detailing the uptake of nicotine and cotinine after chronic nicotine exposure and quantifying the rate of BBB penetration by cotininine, and demonstrating that BBB transfer is not altered by chronic nicotine Exposure. Expand
...
1
2
...