Neurotransmitter receptor
Encyclopedia
A Neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 receptor
is a membrane receptor protein that is activated by a Neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

. A membrane protein
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...

 interacts with the lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...

 that encloses the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 and a membrane receptor protein interacts with a chemical in the cells external environment, which binds to the cell. Membrane receptor proteins, in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

al and glial cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

, allow cells to communicate with one another through chemical signals.

In postsynaptic cells, neurotransmitter receptors receive signals that trigger an electrical signal, by regulating the activity of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s. The binding of neurotransmitters to specific receptors can the membrane potential of a neuron. This can result in a signal that runs along the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

 and can be passed along a neural network
Neural network
The term neural network was traditionally used to refer to a network or circuit of biological neurons. The modern usage of the term often refers to artificial neural networks, which are composed of artificial neurons or nodes...

 (see action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

). On presynaptic cells the binding of a neurotransmitter to a specific receptor provides feedback and mediates excessive neurotransmitter release.

There are two types of Neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 receptors: ligand-gated receptors
Ligand-gated ion channel
Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...

 or ionotropic receptors and G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

s or metabotropic receptors. Ligand-gated receptors can be excited
Excitatory postsynaptic potential
In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...

 by neurotransmitters (ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s) like glutamate
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...

 and aspartate. These receptors can also be inhibited
Inhibitory postsynaptic potential
An inhibitory postsynaptic potential is a synaptic potential that decreases the chance that a future action potential will occur in a postsynaptic neuron or α-motoneuron...

 by neurotransmitters like GABA and glycine
Glycine receptor
The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...

. Conversely, G protein-coupled receptors are neither excitatory nor inhibitory. Rather, they modulate the actions of excititory and inhibitory neurotransmitters. Most neurotransmitters receptors are G-protein coupled.

Ionotropic receptors: Neurotransmitter-Gated Ion Channels

Ligand-gated ion channels (LGICs) are one type of ionotropic receptor or channel-linked receptor
Ion channel linked receptors
Ion channel linked receptors are cell membrane bound receptors. They act through synaptic signaling on electrically excitable cells. The ion channels opening and closing is controlled by neurotransmitters....

. They are a group of transmembrane ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s that are opened or closed in response to the binding of a chemical messenger (i.e., a ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

), such as a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

.

The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric
Allosteric regulation
In biochemistry, allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site . Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are...

 binding site) compared to where the ion conduction pore is located. The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of metabotropic receptor
Metabotropic receptor
Metabotropic receptor is a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells.In the nervous system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors...

s, which use second messenger
Second messenger system
Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus. They relay the signals of hormones like epinephrine , growth factors, and others, and cause some kind of change in the activity of the cell...

s. LGICs are also different from voltage-gated ion channel
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

s (which open and close depending on membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

), and stretch-activated ion channel
Stretch-activated ion channel
Stretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane. Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were...

s (which open and close depending on mechanical deformation of the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

).

Metabotropic Receptors: G-Protein Coupled Receptors

G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 family of transmembrane receptor
Membrane receptor
Cell surface receptors are specialized integral membrane proteins that take part in communication between the cell and the outside world...

s that sense molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

s outside the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 and activate inside signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 pathways and, ultimately, cellular responses. G protein-coupled receptors are found only in eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

s, including yeast, choanoflagellate
Choanoflagellate
The choanoflagellates are a group of free-living unicellular and colonial flagellate eukaryotes considered to be the closest living relatives of the animals...

s, and animals. The ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

 that bind and activate these receptors include light-sensitive compounds, odor
Odor
An odor or odour is caused by one or more volatilized chemical compounds, generally at a very low concentration, that humans or other animals perceive by the sense of olfaction. Odors are also commonly called scents, which can refer to both pleasant and unpleasant odors...

s, pheromone
Pheromone
A pheromone is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting outside the body of the secreting individual to impact the behavior of the receiving individual...

s, hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s, and neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

s, and vary in size from small molecules to peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s to large protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs.

There are two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

 signal pathway and the Phosphatidylinositol
Phosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....

 signal pathway. When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor
Guanine nucleotide exchange factor
Guanine nucleotide exchange factors activate monomeric GTPases by stimulating the release of guanosine diphosphate to allow binding of guanosine triphosphate . A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity...

 (GEF). The GPCR can then activate an associated G-protein by exchanging its bound GDP
Guanosine diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....

 for a GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

. The G-protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13
G12/G13 alpha subunits
G12/G13 subunits are alpha units of heterotrimeric G proteins that regulate cell processes through the use of guanine nucleotide exchange factors. These two subunits represent a fourth class of G protein alpha subunits. They are not sensitive to pertussis toxin.G proteins G12 and G13 regulate...

).

Desensitization and Neurotransmitter Concentration

Neurotransmitter receptors are subject to ligand-induced desensitization: That is, they can become unresponsive upon prolonged exposure to their neurotransmitter. Neurotransmitter receptors are present on both postsynaptic neurons and presynaptic neurons with the former being used to receive neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

s and the latter for the purpose of preventing further release of a given neurotransmitter. In addition to being found in neuron cells, neurotransmitter receptors are also found in various immune and muscle tissues. Many neurotransmitter receptors are categorized as a serpentine receptor or G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 because they span the cell membrane not once, but seven times. Neurotransmitter receptors are known to become unresponsive to the type of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 they receive when exposed for extended periods of time. This phenomenon is known as ligand-induced desensitization or downregulation.

Table of neurotransmitters

Transmitter Molecule Derived From Site of Synthesis
Acetylcholine Choline CNS, parasympathetic nerves
Serotonin (5-HT) Tryptophan CNS, chromaffin cells of the gut, enteric cells
GABA Glutamate CNS
Glutamate CNS
Aspartate CNS
Glycine spinal cord
Histamine Histidine hypothalamus
Epinephrine Tyrosine adrenal medulla, some CNS cells
synthesis pathway
Norpinephrine Tyrosine CNS, sympathetic nerves
synthesis pathway
Dopamine Tyrosine CNS
synthesis pathway
Adenosine ATP CNS, periperal nerves
ATP sympathetic, sensory and enteric nerves
Nitric oxide, NO Arginine CNS, gastrointestinal tract

Example neurotransmitter receptors

  • Adrenergic
    Adrenergic receptor
    The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....


α1A, α1b, α1c, α1d
α2a, α2b, α2c, α2d
β1, β2, β3
  • Dopaminergic
    Dopamine receptor
    Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....


D1, D2, D3, D4, D5
  • GABAergic
    GABA receptor
    The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...


GABAA, GABAB1a, GABAB1δ, GABAB2, GABAC
  • Glutaminergic
    Glutamate receptor
    Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...


NMDA, AMPA kainate, mGluR1, mGluR2, mGluR3, mGluR4, mGluR5, mGluR6, mGluR7
  • Histaminergic
    Histamine receptor
    The histamine receptors are a class of G protein-coupled receptors with histamine as their endogenous ligand.There are four known histamine receptors:*H1 receptor*H2 receptor*H3 receptor*H4 receptor-Comparison:...


H1, H2, H3
  • Cholinergic
    Acetylcholine receptor
    An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...


Muscarinic: M1, M2, M3, M4, M5
Nicotinic: muscle, neuronal (α-bungarotoxin-insensitive), neuronal (α-bungarotoxin-sensitive)
  • Opioid
    Opioid receptor
    Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...


μ, δ1, δ2, κ
  • Serotonergic
    5-HT receptor
    The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission...


5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7
  • Glycinergic
    Glycine receptor
    The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...


Glycine

See also

  • Autoreceptor
    Autoreceptor
    An autoreceptor is a receptor located on presynaptic nerve cell membranes and serves as a part of a feedback loop in signal transduction. It is sensitive only to those neurotransmitters or hormones that are released by the neuron in whose membrane the autoreceptor sits.Canonically, a presynaptic...

  • Heteroreceptor
    Heteroreceptor
    A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own ligand.Heteroreceptors are presynaptic receptors that respond to neurotransmitters, neuromodulators, or neurohormones released from adjacent neurons or cells...

  • Receptor desensitization has been previously modeled in the context of a two-state mathematical model (see this link http://www.bio-balance.com/Graphics.htm)
  • Synaptic Transmission
  • Neuromuscular transmission
  • Catecholamines
  • Cholinergic
    Cholinergic
    The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

     Agonists and Antagonists
    Receptor antagonist
    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...


External links

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