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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/23 18:20:07」(JST)

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

Based on their structural and functional characteristics, the neurotransmitter receptor can be classified into two broad categories: metabotropic and ionotropic receptors. Ionotropic receptors form an ion channel pore. In contrast, metabotropic receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, G protein-coupled receptors are inherently metabotropic. Other examples of metabotropic receptors include tyrosine kinases and 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, are 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 either open or close channels in the cell membrane. 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 tissue". Human Anatomy & Physiology. San Francisco: Pearson Benjamin Cummings. ISBN 0-8053-5910-9.
^ ^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

The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum.

Fatemi SH1,2, Folsom TD1, Liesch SB1, Kneeland RE1, Karkhane Yousefi M1,3, Thuras PD4.
Journal of neuroscience research.J Neurosci Res.2017 May;95(5):1110-1122. doi: 10.1002/jnr.23949. Epub 2016 Oct 13.
PMID 27735078

Glutamate affects the production of epoxyeicosanoids within the brain: The up-regulation of brain CYP2J through the MAPK-CREB signaling pathway.

Liu M1, Zhu Q2, Wu J1, Yu X1, Hu M3, Xie X1, Yang Z1, Yang J1, Feng YQ2, Yue J4.
Toxicology.Toxicology.2017 Apr 15;381:31-38. doi: 10.1016/j.tox.2017.02.008. Epub 2017 Feb 23.
PMID 28237619

Metabotropic glutamate receptor 5 responses dictate differentiation of neural progenitors to NMDA-responsive cells in fragile X syndrome.

Achuta VS1, Grym H1, Putkonen N1, Louhivuori V1, Kärkkäinen V2, Koistinaho J2, Roybon L3, Castrén ML1,4.
Developmental neurobiology.Dev Neurobiol.2017 Apr;77(4):438-453. doi: 10.1002/dneu.22419. Epub 2016 Jul 28.
PMID 27411166

Japanese Journal

グループII代謝型グルタミン酸受容体をターゲットとした新規統合失調症治療薬の創製

日吉哲明,茶木茂之,奥山茂
日本薬理學雜誌 = Folia pharmacologica Japonica 140(3), 111-115, 2012-09-01
NAID 10031072050

グループII代謝型グルタミン酸受容体拮抗薬の新規抗うつ薬としての可能性

茶木茂之
日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology 32(4), 219-226, 2012-08-25
NAID 10031055834

The Selective Metabotropic Glutamate 2/3 Receptor Agonist MGS0028 Reverses Isolation Rearing-Induced Abnormal Behaviors in Mice

Ago Yukio,Araki Ryota,Yano Koji [他],KAWASAKI Toshiyuki,CHAKI Shigeyuki,NAKAZATO Atsuro,ONOE Hirotaka,HASHIMOTO Hitoshi,BABA Akemichi,TAKUMA Kazuhiro,MATSUDA Toshio
Journal of pharmacological sciences 118(2), 295-298, 2012-02-20
… This study examined the effect of MGS0028, a selective metabotropic glutamate 2/3 receptor agonist, on abnormal behaviors such as hyperactivity, aggression, and deficits of prepulse inhibition in isolation-reared mice. … These results suggest that the metabotropic glutamate 2/3 receptor agonist, MGS0028, is a potential compound for the treatment of psychiatric disorders. …
NAID 10030455255

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