nicotinic acetylcholine receptor

Examples of nicotinic acetylcholine receptor in the following topics:

• Agonists, Antagonists, and Drugs

  • A nicotinic agonist is a drug that mimics, in one way or another, the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs).
  • Nicotinic acetylcholine receptors are receptors found in the central nervous system, the peripheral nervous systems, and skeletal muscles.
  • The development of nicotinic acetylcholine receptor agonists began in the early 1990's after the discovery of nicotine's positive effects on animal memory.
  • The nicotinic acetylcholine receptor agonist are gaining increasing attention as drug candidates for multiple central nervous system disorders such as Alzheimer's disease, schizophrenia, attention-deficit hyperactivity disorder (ADHD), and nicotine addiction.
  • In 2009 there were at least five drugs on the market that affect the nicotinic acetylcholine receptors.

• Peripheral Motor Endings

  • Acetylcholine diffuses into the synaptic cleft and binds to the nicotinic acetylcholine receptors located on the motor end plate.
  • The depolarization activates L-type, voltage-dependent calcium channels (dihydropyridine receptors) in the T-tubule membrane, which are in close proximity to calcium-release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum.
  • Clinical Example: Myasthenia gravis is an autoimmune disorder in which circulating antibodies block the nicotinic acetylcholine receptors on the motor end plate of the neuromuscular junction.
  • This blockage of acetylcholine receptors causes muscle weakness, often first exhibiting drooping eyelids and expanding to include overall muscle weakness and fatigue.
  • Detailed view of a neuromuscular junction: 1) Presynaptic terminal; 2) Sarcolemma; 3) Synaptic vesicle; 4) Nicotinic acetylcholine receptor; 5) Mitochondrion.

• Parasympathetic Responses

  • The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors.
  • When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of postganglionic neurons.
  • The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.
  • Two different subtypes of nicotinic acetylcholine receptors with alpha and beta subunits.
  • Acetylcholine binding sites are indicated.

• Ionotropic and Metabotropic Receptors

  • Although both ionotropic and metabotropic receptors are activated by neurotransmitters, ionotropic receptors are channel-linked while metabotropic receptors initiate a cascade of molecules via G-proteins.
  • Two types of membrane-bound receptors are activated with the binding of neurotransmitters: ligand-gated ion channels (LGICs) inotropic receptors and metabotropic G- protein coupled receptors.
  • The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor .
  • It consists of a pentamer of protein subunits with two binding sites for acetylcholine which, when bound, alter the receptor's configuration and cause an internal pore to open.
  • Examples of metabotropic receptors include glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors, most serotonin receptors, and receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides, and endocannabinoids.

• Cholinergic Neurons and Receptors

  • When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand-gated sodium channels in the cell membrane.
  • Although acetylcholine induces contraction of skeletal muscle, it acts via a different type of receptor (muscarinic, see ) to inhibit contraction of cardiac muscle fibers.
  • At the same time, acetylcholine acts through nicotinic receptors to excite certain groups of inhibitory interneurons in the cortex, which further dampen cortical activity.
  • The result was also found in Alzheimer's disease patients and smokers after nicotine (an ACh agonist) consumption.
  • This human M2 muscarinic acetylcholine receptor is bound to an antagonist

• Postganglionic Neurons

  • In the parasympathetic division, they are cholinergic and use acetylcholine as their neurotransmitter.
  • The sympathetic fibers: At the synapses within the ganglia, preganglionic neurons release acetylcholine, a neurotransmitter that activates nicotinic acetylcholine receptors on postganglionic neurons.
  • Postganglionic neurons of sweat glands release acetylcholine for the activation of muscarinic receptors.
  • The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors.
  • Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of postganglionic neurons.

• Function and Physiology of the Spinal Nerves

  • Nerves that release acetylcholine are said to be cholinergic.
  • In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter to stimulate muscarinic receptors.
  • Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors.
  • Upper motor neurons release acetylcholine.
  • Acetylcholine is released from the axon terminal knobs of alpha motor neurons and received by postsynaptic receptors (nicotinic acetylcholine receptors) of muscles, thereby relaying the stimulus to contract muscle fibers.

• Types of Neurotransmitters by Function

  • The major types of neurotransmitters include acetylcholine, biogenic amines, and amino acids.  
  • Acetylcholine, which acts on the neuromuscular junction, was the first neurotransmitter identified.
  • Once released, acetylcholine binds to post-synaptic receptors and is degraded by acetylcholinesterase.
  • Acetylcholine-releasing neurons are also found in the central nervous system (CNS).
  • NE, dopamine, and histamine can be excitatory or inhibitory depending on the receptor type.

• Classification of Neurons

  • A neuron releases a neurotransmitter that binds to chemical receptors on the target neuron .
  • The combination of neurotransmitter and receptor properties results in an excitatory, inhibitory, or modulatory change to the target neuron.
  • Glutamate acts on several different types of receptors, and has effects that are largely excitatory.
  • GABA acts on several different classes of receptors, exerting inhibitory effects.
  • Other types of neurons include excitatory motor neurons in the spinal cord that release acetylcholine, and inhibitory spinal neurons that release glycine.

• Alzheimer's Disease

  • The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine.
  • The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.
  • N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21).