A neurotransmitter receptor (also known as a neuroreceptor) is a membrane receptor protein that is activated by a neurotransmitter. Chemicals on the outside of the cell, such as a neurotransmitter, can bump into the cell's membrane, in which there are receptors. If a neurotransmitter bumps into its corresponding receptor, they will bind and can trigger other events to occur inside the cell. Therefore, a membrane

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

is part of the molecular machinery that allows cells to

communicate Communication (from la, communicare, meaning "to share" or "to be in relation with") is usually defined as the transmission of information. The term may also refer to the message communicated through such transmissions or the field of inquir ...

with one another. A neurotransmitter receptor is a class of receptors that specifically binds with neurotransmitters as opposed to other molecules. In

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

cells, neurotransmitter receptors receive signals that trigger an electrical signal, by regulating the activity of ion channels. The influx of ions through ion channels opened due to the binding of neurotransmitters to specific receptors can change the membrane potential of a neuron. This can result in a signal that runs along the

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

(see

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

) and is passed along at a synapse to another neuron and possibly on to a neural network. On

presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

cells, there can be receptor sites specific to the neurotransmitters released by that cell (see

Autoreceptor An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the au ...

), which provide feedback and mediate excessive neurotransmitter release from it. There are two major types of neurotransmitter receptors: ''ionotropic'' and ''metabotropic''.

Ionotropic Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

means that ions can pass through the receptor, whereas

metabotropic A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: met ...

means that a second messenger inside the cell relays the message (i.e. metabotropic receptors do not have channels). There are several kinds of metabotropic receptors, including

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s. Ionotropic receptors are also called

ligand-gated ion channels Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

and they can be activated by neurotransmitters (

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

s) like glutamate and GABA, which then allow specific ions through the membrane. Sodium ions (that are, for example, allowed passage by the

glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...

)

excite Excitation, excite, exciting, or excitement may refer to: * Excitation (magnetic), provided with an electrical generator or alternator * Excite Ballpark, located in San Jose, California * Excite (web portal), web portal owned by IAC * Electron ex ...

the post-synaptic cell, while chloride ions (that are, for example, allowed passage by the GABA receptor)

inhibit Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotr ...

the post-synaptic cell. Inhibition reduces the chance that an

will occur, while excitation increases the chance. Conversely, G-protein-coupled receptors are neither excitatory nor inhibitory. Rather, they can have a broad number of functions such as modulating the actions of excitatory and inhibitory ion channels or triggering a signalling cascade that releases calcium from stores inside the cell. Most neurotransmitters receptors are G-protein coupled.

Localization

Neurotransmitter (NT) receptors are located on the surface of

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

al and

glia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

l cells. At a synapse, one neuron sends messages to the other neuron via neurotransmitters. Therefore, the postsynaptic neuron, the one receiving the message, clusters NT receptors at this specific place in its membrane. NT receptors can be inserted into any region of the neuron's membrane such as dendrites, axons, and the cell body. Receptors can be located in different parts of the body to act as either an inhibitor or an excitatory receptor for a specific Neurotransmitter Goldman, B. (2010, November 17). New imaging method developed at Stanford reveals stunning details of brain connections. In Stanford medicine news center. Retrieved from https://med.stanford.edu/news/all-news/2010/11/new-imaging-method-developed-at-stanford-reveals-stunning-details-of-brain-connections.html. An example of this are the receptors for the neurotransmitter Acetylcholine (ACh), one receptor is located at the neuromuscular junction in skeletal muscle to facilitate muscle contraction (excitation), while the other receptor is located in the heart to slow down heart rate (inhibitory)

Ionotropic receptors: neurotransmitter-gated ion channels

Ligand-gated ion channels Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

(LGICs) are one type of ionotropic receptor or channel-linked receptor. They are a group of

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

ion channels that are opened or closed in response to the binding of a chemical messenger (i.e., a

), such as a neurotransmitter. The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric 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 A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: met ...

s, which use second messengers. LGICs are also different from voltage-gated ion channels (which open and close depending on membrane potential), and

stretch-activated ion channel Mechanosensitive channels, mechanosensitive ion channels or stretch-gated ion channels (not to be confused with mechanoreceptors). They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They a ...

s (which open and close depending on mechanical deformation of the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

Metabotropic receptors: G-protein coupled receptors

G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

(GPCRs), also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

family of

transmembrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral me ...

s that sense

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

s outside the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

and activate inside signal transduction pathways and, ultimately, cellular responses. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors,

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 like hormones outside the body of the secreting individual, to affect the behavio ...

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

s, and neurotransmitters, and vary in size from small molecules to

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

s to large

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 Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

signal pathway and the

phosphatidylinositol Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...

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 factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated struc ...

(GEF). The GPCR can then activate an associated

G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...

by exchanging its bound

GDP Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...

for a GTP. 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 ( G_αs, G_αi/o, G_αq/11, G_α12/13).

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

neurons ''and'' presynaptic neurons with the former being used to receive neurotransmitters 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

because they span the cell membrane not once, but seven times. Neurotransmitter receptors are known to become unresponsive to the type of neurotransmitter they receive when exposed for extended periods of time. This phenomenon is known as ligand-induced desensitization or

downregulation In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...

Example neurotransmitter receptors

The following are some major classes of neurotransmitter receptors:ed. Kebabain, J. W. & Neumeyer, J. L. (1994). "RBI Handbook of Receptor Classification" *

Adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

: α_1A, α_1b, α_1c, α_1d, α_2a, α_2b, α_2c, α_2d, β₁, β₂, β₃ *

Cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...

: **

Muscarinic Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

: M1, M2, M3, M4, M5 **

Nicotinic Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

: muscle, neuronal (α-bungarotoxin-insensitive), neuronal (α-bungarotoxin-sensitive) * Dopaminergic: D₁, D₂, D₃, D₄, D₅ * GABAergic: GABA_A, GABA_B1a, GABA_B1δ, GABA_B2, GABA_C *

Glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonis ...

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

Kainate Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

, mGluR₁, mGluR₂, mGluR₃, mGluR₄, mGluR₅, mGluR₆, mGluR₇ *

Glycinergic A glycinergic agent (or drug) is a chemical which functions to directly modulate the glycine system in the body or brain. Examples include glycine receptor agonists, glycine receptor antagonists, and glycine reuptake inhibitors. See also * Adenos ...

: Glycine *

Histaminergic Histaminergic means "working on the histamine system", and histaminic means "related to histamine". A histaminergic agent (or drug) is a chemical which functions to directly modulate the histamine system in the body or brain. Examples include his ...

: H₁, H₂, H₃ *

Opioidergic An opioidergic agent (or drug) is a chemical which functions to directly modulate the opioid neuropeptide systems (i.e., endorphin, enkephalin, dynorphin, nociceptin) in the body or brain. Examples include opioid analgesics such as morphine a ...

: μ, δ₁, δ₂, κ *

Serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

: 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1E, 5-HT_1F, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, 5-HT₇

Notes and references

External links

Brain Explorer

Snyder (2009) Neurotransmitters, Receptors, and Second Messengers Galore in 40 Years. Journal of Neuroscience. 29(41): 12717-12721.Snyder and Bennett (1976) Neurotransmitter Receptors in the Brain: Biochemical Identification. Annual Review of Physiology. Vol. 38: 153-175Library of Congress Authorities and Vocabularies: Neurotransmitter ReceptorsNeurotransmitter Receptors, Transporters, & Ion Channels
* {{DEFAULTSORT:Neurotransmitter Receptor Receptors Behavioural genetics he:קולטן#הקולטן העצבי