Central nervous system nicotinic acetylcholine receptors

Orth M, Amann B, Robertson MM, RothweU JC (2005) ExcitabUity of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine. Brain 128 1292-1300 Oswald RE, Freeman JA (1981) Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors. Neuroscience 6 1-14... 

Histrionicotoxin, 342, and synthetic analog inhibition of ligand binding at sites associated with the sodium, potassium, and calcium channels in brain membrane preparations has been investigated [721]. The effects of 342 on the ion channel of central nervous system nicotinic acetylcholine receptors [722], and on post-tetanic potentiation of mouse and rat phrenic nerve diaphram preparations have been described [723]. 

In the central nervous system muscarinic acetylcholine receptors are more abundant than nicotinic receptors. They consist of single-chain proteins of mass 70 kDa. They are not ion channels but are 7-helix receptors homologous in sequence with P-adrenergic receptors (Fig. 11-6) and with rhodopsin.648 Five different subtypes (M1-M5) have been characterized. 

Cholinergic Transmission is the process of synaptic transmission which uses mainly acetylcholine as a transmitter. Cholinergic transmission is found widely in the peripheral and central nervous system, where acetylcholine acts on nicotinic and muscarinic receptors. 

Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscurinic and nicotinic acetylcholine receptors, N-methyl-D-aspartate (NMDA) receptors and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant impramine and in massive overdose may affect cardiac sodium channels. 

Mode of Motion. Nicotine, anabasine, and imidocloprid affect the ganglia of the insect central nervous system, faciUtating transsynaptic conduction at low concentrations and blocking conduction at higher levels. The extent of ionisation of the nicotinoids plays an important role in both their penetration through the ionic barrier of the nerve sheath to the site of action and in their interaction with the site of action, which is befleved to be the acetylcholine receptor protein. There is a marked similarity in dimensions between acetylcholine and the nicotinium ion. 

Neonicotinoids are potent broad-spectrum insecticides that exhibit contact, stomach and systemic activity. Acetamiprid, imidacloprid, nitenpyram, thiamethoxam and thiacloprid are representatives of the neonicotinoid insecticides (Figure 1). The mechanism of action is similar to that of nicotine, acting on the central nervous system causing irreversible blocking of postsynaptic nicotinic acetylcholine receptors (nAChR). Neonicotinoid insecticides are often categorized as antagonists of the... 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

Vallejo YE, Buisson B, Bertrand D, Green WN (2005) Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism. J Neurosci 25 5563-5572 Vemino S, Amador M, Luetje CW, Patrick J, Dani JA (1992) Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron 8 127-134 Vizi ES, Lendvai B (1999) Modulatory role of presynaptic nicotinic receptors in synaptic and non-synaptic chemical communication in the central nervous system. Brain Res Brain Res Rev 30 219-235... 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

There is considerable diversity among nicotinic acetylcholine receptors, and at least one source of this diversity is the multiplicity of acetylcholine receptor genes. Cholinergic-nicotinic receptors in skeletal muscle are different from those in autonomic ganglia and the central nervous system. 

Mecfianism of Action A cholinergic-receptor agonist that binds to acetylcholine receptors, producing both stimulating and depressant effects on the peripheral and central nervous systems. Therapeutic Effect Provides a source of nicotine during nicotine withdrawal and reduces withdrawal symptoms. 

Skeletal muscle relaxation and paralysis can occur from interruption of function at several sites along the pathway from the central nervous system (CNS) to myelinated somatic nerves, unmyelinated motor nerve terminals, nicotinic acetylcholine receptors, the motor end plate, the muscle membrane, and the intracellular muscular contractile apparatus itself. 

Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system. Inhibition of acetylcholinesterase results in accumulation of acetylcholine at muscarinic and nicotinic receptors leading to peripheral and central nervous system effects. These effects... 

Nicotine is known to bind to acetylcholine receptors (the receiving areas on cells) that are located throughout the central nervous system as well as the peripheral nervous system. Acetylcholine is a neurotransmitter it transmits nerve impulses from one nerve fiber to another. The pleasurable effects of nicotine are a... 

The nicotinic acetylcholine (ACh) receptor is a well-characterized receptor of this type consisting of five subunits. It is present on the skeletal muscle cell end-plate in the neuromuscular junction, at all autonomic ganglia, and in the central nervous system (CNS). The function of this receptor is to convert ACh binding into an electrical signal via increased Na+ or K+ permeability across the cell membrane (i.e., membrane depolarization). When two molecules of ACh bind to the a subunit of the receptor, a conformational change in the receptor induces opening of the channel to at least 0.65 nm for approximately 1-2 ms. 

Dani JA, Bertrand D. 2007. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 47 699-729. 

---