Metabotropní glutamátový receptor

Metabotropní glutamátový receptor (mGluR), je typem glutamátového receptoru, který je aktivní skrze nepřímý metabotropní proces. Patří mezi receptory spřažené s G proteinem.[1] Všechny glutamátové receptory se vážou na glutamát jako na excitační neurotransmiter.

Kyselina glutamová

Funkce a struktura

Na rmGluR receptorech probíhají různé funkce nervového systému (učení, paměť, úzkost, a vnímání bolesti),[2] nacházejí se v pre- i postsynaptických neuronech, v synapsích v hipokampu, mozečku,[3] a mozkové kůře, stejně jako v jiných částech mozku a v periferních tkáních.[4]

Stejně jako ostatní metabotropní receptory mají sedm transmembránových domén, které se klenou přes buněčnou membránu a[5] na rozdíl od ionotropních receptorů nejsou iontovými kanály. Aktivují biochemické kaskády, tím modifikují proteiny, jako například iontové kanály.[6] Ovlivňují dráždivost synapse, např. způsobují presynaptickou inhibicí neurotransmise,[7] nebo modulují, případně vyvolávají postsynaptickou odpověď.[8] Dimerní organizace mGluRs je nutná pro signalizaci vyvolanou agonistou.[9]

Klasifikace

Osm různých typů (mGluR1 až mGluR8) je rozděleno do skupin I, II, a III. podle struktury a fyziologické aktivity.[2] mGluRs se dále dělí na podtypy, mGluR7a a mGluR7b.

Skupina receptoy působení aktivita funkce
Skupina I Gq mGluR 1

mGluR 5

postsynapticky zvýšení aktivity NMDA receptorů a riziko excitotoxicity kromě aktivace PLC také přímý vliv na draslíkovové a vápníkové kanály
Skupina II Gi/o mGluR2

mGluR3

presynapticky snížení aktivity NMDA receptorů a riziko excitotoxicity agonisté mají potenciální využití v léčbě schizofrenie
Skupina III Gi/o mGluR4

mGluR6

mGluR7

mGluR8

presynapticky snížení aktivity NMDA receptorů a riziko excitotoxicity

Reference

V tomto článku byl použit překlad textu z článku Metabotropic glutamate receptor na anglické Wikipedii.

  1. ↑ Bonsi P, Cuomo D, De Persis C, Centonze D, Bernardi G, Calabresi P, Pisani A. Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluR1 function in striatal cholinergic interneurons. Neuropharmacology. 2005, s. 104–13. doi:10.1016/j.neuropharm.2005.05.012. PMID 16005029. 
  2. ↑ a b Ohashi H, Maruyama T, Higashi-Matsumoto H, Nomoto T, Nishimura S, Takeuchi Y. A novel binding assay for metabotropic glutamate receptors using [³H] L-quisqualic acid and recombinant receptors. Zeitschrift für Naturforschung C. 2002, s. 348–55. Dostupné online. doi:10.1515/znc-2002-3-425. PMID 12064739. 
  3. ↑ Hinoi E, Ogita K, Takeuchi Y, Ohashi H, Maruyama T, Yoneda Y. Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues. Neurochemistry International. March 2001, s. 277–85. doi:10.1016/S0197-0186(00)00075-9. PMID 11099787. 
  4. ↑ Chu Z, Hablitz JJ. Quisqualate induces an inward current via mGluR activation in neocortical pyramidal neurons. Brain Research. October 2000, s. 88–92. doi:10.1016/S0006-8993(00)02752-9. PMID 11011009. 
  5. ↑ Platt SR. The role of glutamate in central nervous system health and disease--a review. Veterinary Journal. March 2007, s. 278–86. doi:10.1016/j.tvjl.2005.11.007. PMID 16376594. 
  6. ↑ Gabriel L, Lvov A, Orthodoxou D, Rittenhouse AR, Kobertz WR, Melikian HE. The acid-sensitive, anesthetic-activated potassium leak channel, KCNK3, is regulated by 14-3-3β-dependent, protein kinase C (PKC)-mediated endocytic trafficking. The Journal of Biological Chemistry. September 2012, s. 32354–66. doi:10.1074/jbc.M112.391458. PMID 22846993. 
  7. ↑ Sladeczek F., Momiyama A.,Takahashi T. (1992). "Presynaptic inhibitory action of metabotropic glutamate receptor agonist on excitatory transmission in visual cortical neurons". Proc. Roy. Soc. Lond. B 1993 253, 297-303.
  8. ↑ Endoh T. Characterization of modulatory effects of postsynaptic metabotropic glutamate receptors on calcium currents in rat nucleus tractus solitarius. Brain Research. October 2004, s. 212–24. doi:10.1016/j.brainres.2004.07.074. PMID 15451384. 
  9. ↑ El Moustaine D, Granier S, Doumazane E, Scholler P, Rahmeh R, Bron P, Mouillac B, Banères JL, Rondard P, Pin JP. Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proceedings of the National Academy of Sciences of the United States of America. October 2012, s. 16342–7. doi:10.1073/pnas.1205838109. PMID 22988116. 

Externí odkazy

Transmembránové receptory
Receptor spřažený s G proteinem
Třída A
Třída B
Třída C
Třída D
Třída E
Třída F
Ionotropní receptor
Katalytický receptor
Ostatní

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