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Related Concept Videos

Cholinergic Receptors: Nicotinic01:15

Cholinergic Receptors: Nicotinic

Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Cholinergic Receptors: Muscarinic01:25

Cholinergic Receptors: Muscarinic

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic antagonists are called...
Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants


Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...

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Related Experiment Video

Updated: Jun 6, 2026

Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
09:06

Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells

Published on: December 19, 2025

Targeted Mutations Activate Allosteric Modulation of α5-Containing Nicotinic Acetylcholine Receptors.

Christopher B Marotta1, Henry A Lester2, Dennis A Dougherty1

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.

ACS Chemical Neuroscience
|June 4, 2026
PubMed
Summary

Researchers investigated the alpha5 subunit of nicotinic acetylcholine receptors, crucial for neuronal communication and nicotine dependence. Mutating the alpha5 subunit did not yield direct activation but allowed modulation of receptor signals using a positive allosteric modulator.

Keywords:
NS9283alpha5 (α5)cytisinenicotinenicotinic acetylcholine receptorspositive allosteric modulator

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Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking
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Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking

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Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
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Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking

Published on: March 16, 2017

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Nicotinic acetylcholine receptors (nAChRs) are critical for neuronal signaling.
  • The alpha5 subunit uniquely occupies an auxiliary position in nAChRs, significantly impacting receptor function.
  • Alpha5 subunit expression in reward and aversion pathways underscores its role in nicotine dependence.

Purpose of the Study:

  • To investigate the functional consequences of mimicking alpha4 residues within the alpha5 subunit's agonist binding site.
  • To explore the potential for small molecule modulation at the alpha5-alpha4 interface.
  • To understand the role of the alpha5 subunit in receptor activation and signaling.

Main Methods:

  • Site-directed mutagenesis of the alpha5 nicotinic acetylcholine receptor subunit.
  • Testing receptor activation with various agonists, including acetylcholine, nicotine, and cytisine.
  • Evaluation of receptor signal modulation using the positive allosteric modulator NS9283.

Main Results:

  • Mutating the alpha5 subunit to mimic alpha4 residues did not result in direct agonist activation.
  • No direct activation was observed with acetylcholine, nicotine, or cytisine.
  • The positive allosteric modulator NS9283 successfully modulated the receptor signal response.

Conclusions:

  • The alpha5 subunit's unique structural position influences receptor pharmacology.
  • Direct activation of the mutated alpha5 subunit by conventional agonists is not achieved.
  • Positive allosteric modulation offers a viable strategy to influence nAChR function involving the alpha5 subunit.