Metabotropic receptor
Encyclopedia
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. In contrast to the latter, metabotropic receptors do not form an ion channel pore; rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction
mechanisms, often G protein
s. Hence, they are a type of G protein-coupled receptor
. Others are tyrosine kinases
or guanylyl cyclase receptors.
What both receptor types have in common is that they are activated by specific neurotransmitters. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na+, K+, or Cl- to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that can also results in ion channel opening but must involve a range of second messenger chemicals.
s, muscarinic acetylcholine receptor
s, GABAB receptors, and most serotonin
receptors, as well as receptors for norepinephrine
, epinephrine
, histamine
, dopamine
, neuropeptide
s (Austin, 2004; Purves et al., 2001) and endocannabinoids.
The 7 transmembrane spanning domains, with an external amino terminus, is often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of ~ 450-550 amino acids.
s as ligands
, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand, also called the primary messenger, binds to the receptor, or the transducer, the latter activates a primary effector, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of molecule
s in turn, channels associated with these receptors take longer to open than ionotropic receptors do, and they are thus not involved in mechanisms that require quick responses (Kandel et al., 2000, p. 240). However, metabotropic receptors also remain open from seconds to minutes (Kandel et al., 2000, p. 250-251). Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds (Austin, 2004). While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread through the cell.
Metabotropic receptors can both open and close channels. They can make a membrane more excitable by closing K+ channel
s, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an action potential
(Kandel et al., 2000, p. 242-243). Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic neuron
(Schmitz et al., 2001). These receptors can be further classified into receptor tyrosine kinase
s and G protein-coupled receptor
s, or GPCRs (Kandel et al., 2000, p. 229)..
In the nervous system, based on their structural and functional characteristics, 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
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
can be classified into two broad categories: metabotropic and ionotropic receptors. In contrast to the latter, metabotropic receptors do not form an ion channel pore; rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through 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...
mechanisms, often G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
s. Hence, they are a type of 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...
. Others are tyrosine kinases
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
or guanylyl cyclase receptors.
What both receptor types have in common is that they are activated by specific neurotransmitters. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na+, K+, or Cl- to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that can also results in ion channel opening but must involve a range of second messenger chemicals.
Examples
This class of receptors includes the metabotropic glutamate receptorMetabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs...
s, muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s, GABAB receptors, and most serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
receptors, as well as receptors for norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
s (Austin, 2004; Purves et al., 2001) and endocannabinoids.
Structure
The G protein-coupled receptors have seven hydrophobic transmembrane domains. Most of them are monomeric proteins, although GABAB receptors require heterodimerization to function properly. The protein's N terminus is located on the extracellular side of the membrane and its C terminus is on the intracellular side (Purves et al., 2001).The 7 transmembrane spanning domains, with an external amino terminus, is often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of ~ 450-550 amino acids.
Function
Metabotropic receptors have neurotransmitterNeurotransmitter
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 as 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...
, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand, also called the primary messenger, binds to the receptor, or the transducer, the latter activates a primary effector, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of 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 in turn, channels associated with these receptors take longer to open than ionotropic receptors do, and they are thus not involved in mechanisms that require quick responses (Kandel et al., 2000, p. 240). However, metabotropic receptors also remain open from seconds to minutes (Kandel et al., 2000, p. 250-251). Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds (Austin, 2004). While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread through the cell.
Metabotropic receptors can both open and close channels. They can make a membrane more excitable by closing K+ channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
s, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an 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...
(Kandel et al., 2000, p. 242-243). Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic 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...
(Schmitz et al., 2001). These receptors can be further classified into receptor tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
s 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 GPCRs (Kandel et al., 2000, p. 229)..