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.

• 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.

• Classification of Receptors by Stimulus

  • Sensory receptors can be classified by the type of stimulus that generates a response in the receptor.
  • Sensory receptors perform countless functions in our bodies.
  • Cutaneous receptors are sensory receptors found in the dermis or epidermis.
  • Encapsulated receptors consist of the remaining types of cutaneous receptors.
  • A tonic receptor is a sensory receptor that adapts slowly to a stimulus, while a phasic receptor is a sensory receptor that adapts rapidly to a stimulus.

• Blocking of Hormone Receptors

  • A receptor antagonist does not provoke a biological response upon receptor binding, but limits or dampens agonist-mediated responses.
  • A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses.
  • Binding to the active site on the receptor regulates receptor activation directly.
  • The current accepted definition of receptor antagonist is based on the receptor occupancy model.
  • Irreversible antagonists covalently bind to the receptor target and, in general, cannot be removed; inactivating the receptor for the duration of the antagonist effects is determined by the rate of receptor turnover, the rate of synthesis of new receptors.

• Lung Cancer

  • Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.
  • The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.