The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors

Over the past two decades, combustible cigarette smoking has slowly declined by nearly 11% in America; however, the use of electronic cigarettes has increased tremendously, including among adolescents. While nicotine is the main addictive component of tobacco products and a primary concern in electronic cigarettes, this is not the only constituent of concern. There is a growing market of flavored products and a growing use of zero-nicotine e-liquids among electronic cigarette users. Accordingly, there are few studies that examine the impact of flavors on health and behavior. Menthol has been studied most extensively due to its lone exception in combustible cigarettes. Thus, there is a broad understanding of the neurobiological effects that menthol plus nicotine has on the brain including enhancing nicotine reward, altering nicotinic acetylcholine receptor number and function, and altering midbrain neuron excitability. Although flavors other than menthol were banned from combustible cigarettes, over 15,000 flavorants are available for use in electronic cigarettes. This review seeks to summarize the current knowledge on nicotine addiction and the various brain regions and nicotinic acetylcholine receptor subtypes involved, as well as describe the most recent findings regarding menthol and green apple flavorants, and their roles in nicotine addiction and vaping-related behaviors.

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Firing responses mediated via distinct nicotinic acetylcholine receptor subtypes in rat prepositus hypoglossi nuclei neurons

Journal of Neurophysiology ◽

10.1152/jn.00168.2018 ◽

2018 ◽

Vol 120 (4) ◽

pp. 1525-1533

Author(s):

Yue Zhang ◽

Yuchio Yanagawa ◽

Yasuhiko Saito

Keyword(s):

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Firing Frequency ◽

Membrane Properties ◽

Receptor Subtypes ◽

Nicotinic Acetylcholine ◽

Firing Patterns ◽

Prepositus Hypoglossi ◽

Specific Antagonist ◽

The Relationship

We previously reported that cholinergic current responses mediated via nicotinic acetylcholine (ACh) receptors (nAChRs) in the prepositus hypoglossi nucleus (PHN), which participates in gaze control, can be classified into distinct types based on different kinetics and are mainly composed of α7- and/or non-α7-subtypes: fast (F)-, slow (S)-, and fast and slow (FS)-type currents. In this study, to clarify how each current type is related to neuronal activities, we investigated the relationship between the current types and the membrane properties and the firing responses that were induced by each current type. The proportion of the current types differed in neurons that exhibited different afterhyperpolarization (AHP) profiles and firing patterns, suggesting that PHN neurons show a preference for specific current types dependent on the membrane properties. In response to ACh, F-type neurons showed either one action potential (AP) or multiple APs with a short firing duration, and S-type neurons showed multiple APs with a long firing duration. The firing frequency of F-type neurons was significantly higher than that of S-type and FS-type neurons. An α7-subtype-specific antagonist abolished the firing responses of F-type neurons and reduced the responses of FS-type neurons but had little effect on the responses of S-type neurons, which were reduced by a non-α7-subtype-specific antagonist. These results suggest that the different properties of the current types and the distinct expression of the nAChR subtypes in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs. NEW & NOTEWORTHY Prepositus hypoglossi nucleus (PHN) neurons show distinct nicotinic acetylcholine receptor (nAChR)-mediated current responses. The proportion of the current types differed in the neurons that exhibited different afterhyperpolarization profiles and firing patterns. The nAChR-mediated currents with different kinetics induced firing responses of the neurons that were distinct in the firing frequency and duration. These results suggest that the different properties of the current types in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs.

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Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

Journal of Experimental Biology ◽

10.1242/jeb.208.16.3219 ◽

2005 ◽

Vol 208 (16) ◽

pp. 3219-3219

Keyword(s):

Nervous System ◽

Guinea Pig ◽

Enteric Nervous System ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Receptor Subtypes ◽

Optical Studies ◽

Nicotinic Acetylcholine

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Expression of nicotinic acetylcholine receptor subtypes in brain and retina

Molecular Brain Research ◽

10.1016/0169-328x(91)90057-5 ◽

1991 ◽

Vol 10 (1) ◽

pp. 61-70 ◽

Cited By ~ 80

Author(s):

P.J. Whiting ◽

R. Schoepfer ◽

W.G. Conroy ◽

M.J. Gore ◽

K.T. Keyser ◽

...

Keyword(s):

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Receptor Subtypes ◽

Nicotinic Acetylcholine

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Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by α-Conotoxin GID and Analogues

Journal of Biological Chemistry ◽

10.1074/jbc.m804950200 ◽

2008 ◽

Vol 284 (8) ◽

pp. 4944-4951 ◽

Cited By ~ 30

Author(s):

Emma L. Millard ◽

Simon T. Nevin ◽

Marion L. Loughnan ◽

Annette Nicke ◽

Richard J. Clark ◽

...

Keyword(s):

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Neuronal Nicotinic Acetylcholine Receptor ◽

Receptor Subtypes ◽

Nicotinic Acetylcholine

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Role of the α7 Nicotinic Acetylcholine Receptor in the Pathophysiology of Atherosclerosis

Frontiers in Physiology ◽

10.3389/fphys.2020.621769 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ildernandes Vieira-Alves ◽

Leda M. C. Coimbra-Campos ◽

Maria Sancho ◽

Rafaela Fernandes da Silva ◽

Steyner F. Cortes ◽

...

Keyword(s):

Immune Function ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Immune Cells ◽

Current Knowledge ◽

Atheromatous Plaque ◽

Inflammatory Disorder ◽

Α7 Nicotinic Acetylcholine Receptor ◽

Nicotinic Acetylcholine ◽

Progression Of Atherosclerosis

Atherosclerosis constitutes a major risk factor for cardiovascular diseases, the leading cause of morbidity and mortality worldwide. This slowly progressing, chronic inflammatory disorder of large- and medium-sized arteries involves complex recruitment of immune cells, lipid accumulation, and vascular structural remodeling. The α7 nicotinic acetylcholine receptor (α7nAChR) is expressed in several cell types involved in the genesis and progression of atherosclerosis, including macrophages, dendritic cells, T and B cells, vascular endothelial and smooth muscle cells (VSMCs). Recently, the α7nAChR has been described as an essential regulator of inflammation as this receptor mediates the inhibition of cytokine synthesis through the cholinergic anti-inflammatory pathway, a mechanism involved in the attenuation of atherosclerotic disease. Aside from the neuronal cholinergic control of inflammation, the non-neuronal cholinergic system similarly regulates the immune function. Acetylcholine released from T cells acts in an autocrine/paracrine fashion at the α7nAChR of various immune cells to modulate immune function. This mechanism additionally has potential implications in reducing atherosclerotic plaque formation. In contrast, the activation of α7nAChR is linked to the induction of angiogenesis and VSMC proliferation, which may contribute to the progression of atherosclerosis. Therefore, both atheroprotective and pro-atherogenic roles are attributed to the stimulation of α7nAChRs, and their role in the genesis and progression of atheromatous plaque is still under debate. This minireview highlights the current knowledge on the involvement of the α7nAChR in the pathophysiology of atherosclerosis.

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