nicotinic receptors

Examples of nicotinic receptors in the following topics:

• 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 the 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 are shown.

• 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 nineties after the discovery of nicotine's positive effects on animal memory.
  • The nicotinic acetylcholine receptor agonists 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.

• Neurotransmitters

  • The cholinergic system has two types of receptors: the nicotinic receptor and the acetylcholine receptor, which is known as the muscarinic receptor.
  • Both of these receptors are named for chemicals that interact with the receptor in addition to the neurotransmitter acetylcholine.
  • Nicotine, the chemical in tobacco, binds to the nicotinic receptor and activates it similarly to acetylcholine.
  • However, they cannot bind to each others' receptors.
  • When acetylcholine binds to the nicotinic receptor, the postsynaptic cell is depolarized.

• 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.

• Postganglionic Neurons

  • At the synapses within the ganglia, the preganglionic neurons release acetylcholine, a neurotransmitter that activates nicotinic acetylcholine receptors on postganglionic neurons.
  • The activation of target tissue receptors causes the effects associated with the sympathetic system.
  • 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 the nicotinic receptors of the postganglionic neurons.
  • The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.

• Cholinergic Neurons and Receptors

  • When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand-gated sodium channels in the cell membrane.
  • At the same time, acetylcholine acts through nicotinic receptors to excite certain groups of inhibitory interneurons in the cortex that 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 (ACh).
  • Homomeric receptors contain 5 identical subunits and have 5 binding sites located at the interfaces between adjacent subunits.

• Function and Physiology of the Spinal Nerves

  • 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.
  • 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.

• 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 .
  • 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.
  • Since opening channels by metabotropic receptors involves activating a number of molecules in the intracellular mechanism, these receptors take longer to open than the inotropic receptors.

• Regulatory Proteins

  • During stimulation of the muscle cell, the motor neuron releases the neurotransmitter acetylcholine, which then binds to a post-synaptic nicotinic acetylcholine receptor.
  • A change in the receptor conformation causes an action potential, activating voltage-gated L-type calcium channels, which are present in the plasma membrane.
  • The inward flow of calcium from the L-type calcium channels activates ryanodine receptors to release calcium ions from the sarcoplasmic reticulum.
  • It is not understood whether the physical opening of the L-type calcium channels or the presence of calcium causes the ryanodine receptors to open.

• Stimulants

  • Others block the action of certain receptors (such as the adenosine receptors) in a process known as receptor antagonism.
  • Still others cause action in other receptors (such as nicotinic acetylcholine) in a process known as receptor agonism.
  • Examples of well-known stimulants include amphetamines, MDMA, NDRIs, cocaine, caffeine, and nicotine.
  • In very low concentrations, nicotine also acts as a stimulant, and it is one of the main factors responsible for the dependence-forming properties of tobacco.