関: G protein-coupled receptors

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

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=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/28 16:37:49」(JST)

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A metabotropic receptor is a type of membrane receptors of eukaryotic cells that acts through a second messenger. It may be located at the surface of the cell or in vesicles.

In the cardiac system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors. Ionotropic receptors form an ion channel pore. Metabotropic receptors do not. Rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, they are a type of G protein-coupled receptor. Others are tyrosine kinases or guanylyl cyclase receptors.

Both receptor types 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 result in ion channels opening but must involve a range of second messenger chemicals.

Examples

This class of receptors includes the metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABA_B receptors, and most serotonin receptors, as well as receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides^[1]^[2] and endocannabinoids.

Structure

The G protein-coupled receptors have seven hydrophobic transmembrane domains. Most of them are monomeric proteins, although GABA_B 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.^[2]

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 neurotransmitters as ligands, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand (the neurotransmitter) binds to the receptor (the transducer) the latter activates a primary effector via the G-protein, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of molecules 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.^[3]^:240 However, metabotropic receptors also remain open from seconds to minutes.^[3]^:250–1 Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds.^[1] 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⁺ channels, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an action potential.^[3]^:242–3 Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic neuron.^[4] These receptors can be further classified into receptor tyrosine kinases and G protein-coupled receptors, or GPCRs.^[3]^:229

References

^ ^a ^b Hoehn K, Marieb EN (2007). "Fundamentals of the nervous system and nervous". Human Anatomy & Physiology. San Francisco: Pearson Benjamin Cummings. ISBN 0-8053-5910-9. http://wps.aw.com/bc_marieb_happlace_7_oa/42/10967/2807754.cw/index.html.
^ ^a ^b Williams, S. J.; Purves, Dale (2001). Neuroscience. Sunderland, Mass: Sinauer Associates. ISBN 0-87893-742-0.
^ ^a ^b ^c ^d Jessell TM, Kandel ER, Schwartz JH (2000). Principles of Neural Science. New York: McGraw-Hill. ISBN 0-8385-7701-6.
^ Schmitz D, Mellor J, Nicoll RA (March 2001). "Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses". Science 291 (5510): 1972–6. doi:10.1126/science.1057105. PMID 11239159.

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English Journal

Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ.

Langer J, Stephan J, Theis M, Rose CR.SourceInstitute of Neurobiology, Heinrich-Heine-University Duesseldorf, Universitätsstrasse 1, Duesseldorf, Germany.
Glia.Glia.2012 Feb;60(2):239-52. doi: 10.1002/glia.21259. Epub 2011 Oct 24.
Activation of glutamatergic synapses results in long-lasting sodium transients in astrocytes mediated mainly by sodium-dependent glutamate uptake. Sodium elevations activate Na(+) /K(+) -ATPase and glucose uptake by astrocytes, representing key signals for coupling glial metabolism to neuronal activ
PMID 22025386

Counteracting roles of metabotropic glutamate receptor subtypes 1 and 5 in regulation of pain-related spatial and temporal synaptic plasticity in rat entorhinal-hippocampal pathways.

Liu MG, Lu D, Wang Y, Chen XF, Li Z, Xu Y, Jin JH, Wang RR, Chen J.SourceInstitute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, China.
Neuroscience letters.Neurosci Lett.2012 Jan 17;507(1):38-42. Epub 2011 Dec 7.
It was previously found that persistent inflammatory pain state resulted in enhancement of synaptic connections and efficacy in direct entorhinal-hippocampal (EC-HIP) pathways. In the current study, the roles of two subtypes of group I metabotropic glutamate receptors in the above processes were eva
PMID 22172929

Japanese Journal

Extracellular ATP modulates synaptic plasticity induced by activation of metabotropic glutamate receptors in the hippocampus

,
Biomedical Research 36(1), 1-9, 2015
… It has been known that the metabotropic glutamate receptor (mGluR) is required for persistent forms of memory and induction of synaptic plasticity. … The direction of the mGluR-induced synaptic plasticity, i.e., either long-term potentiation (LTP) or long-term-depression (LTD), is dependent on whether N-methyl-D-aspartate receptors (NMDARs) are co-activated with mGluRs. …
NAID 130004903878

Regulation and functional roles of rebound potentiation at cerebellar stellate cell—Purkinje cell synapses

Hirano Tomoo,Kawaguchi Shin-ya
Frontiers in Cellular Neuroscience 8, 2014-02-18
… Whether RP is induced or not is determined by the balance between phosphorylation and de-phosphorylation activities regulated by intracellular Ca[2+] and by metabotropic GABA and glutamate receptors. …
NAID 120005385884

N–acetylaspartylglutamate（NAAG）と痛み

山本達郎
PAIN RESEARCH 29(4), 205-213, 2014
… N–acetyl–aspartyl–glutamate (NAAG) is the most prevalent and widely distributed peptide transmitter in the mammalian nervous system.NAAG acts as an agonist at metabotropic glutamate receptor 3 (mGluR3). … Metabotropic GluRs have been identified as significant analgesic targets. … Glutamate, a metabolite of NAAG, may act as a neurotransmitter and activate glutamate receptors such as NMDA receptor and other type of mGluRs. …
NAID 130004839649