Editing GABA receptor (section)

==G protein-coupled receptors==

===GABA<sub>B</sub> receptor===
{{Main|GABAB receptor}}

A slow response to GABA is mediated by [[GABA B receptor|GABA<sub>B</sub> receptors]],<ref name="pmid12037141">{{cite journal |vauthors=Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M, Bonner TI, Enna SJ | title = International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function | journal = Pharmacological Reviews | volume = 54 | issue = 2 | pages = 247–64 |date=June 2002 | pmid = 12037141 | doi = 10.1124/pr.54.2.247  | s2cid = 86015084 }}</ref> originally defined on the basis of pharmacological properties.<ref name="pmid6243177">{{cite journal |vauthors=Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss DN, Shaw J, Turnbull M | title = (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor | journal = Nature | volume = 283 | issue = 5742 | pages = 92–4 |date=January 1980 | pmid = 6243177 | doi = 10.1038/283092a0 | bibcode = 1980Natur.283...92B | s2cid = 4238700 }}</ref>

In studies focused on the control of neurotransmitter release, it was noted that a GABA receptor was responsible for modulating evoked release in a variety of isolated tissue preparations. This ability of GABA to inhibit neurotransmitter release from these preparations was not blocked by bicuculline, was not mimicked by [[isoguvacine]], and was not dependent on Cl¯, all of which are characteristic of the [[GABA A receptor|GABA<sub>A</sub>]] receptor. The most striking discovery was the finding that [[baclofen]] (β-parachlorophenyl GABA), a clinically employed muscle relaxant<ref name="Bein">{{cite book | author = Bein HJ | editor = Birkmayer W | title = Spasticity: A Topical Survey | publisher = Hans Hubert Bern, Switzerland | year = 1972 | chapter = Pharmacological differentiations of muscle relaxants | pages = 76–89 | isbn = 3-456-00390-0 }}</ref><ref name="Keberle">{{cite book |vauthors=Keberle H, Faigle JW | editor = Birkmayer W | title = Spasticity: A Topical Survey | publisher = Hans Hubert Bern, Switzerland | year = 1972 | chapter = Synthesis and structure-activity relationship of the gamma-aminobutyric acid derivatives | pages = 76–89 | isbn = 3-456-00390-0 }}</ref> mimicked, in a [[stereoselective]] manner, the effect of GABA.

Later ligand-binding studies provided direct evidence of binding sites for baclofen on central neuronal membranes.<ref name="pmid6259535">{{cite journal |vauthors=Hill DR, Bowery NG | title = 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain | journal = Nature | volume = 290 | issue = 5802 | pages = 149–52 |date=March 1981 | pmid = 6259535 | doi = 10.1038/290149a0 | bibcode = 1981Natur.290..149H | s2cid = 4335907 }}</ref> [[cDNA]] cloning confirmed that the GABA<sub>B</sub> receptor belongs to the family of [[G-protein-coupled receptor|G-protein coupled receptors]].<ref name="pmid9069281">{{cite journal |vauthors=Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B | title = Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors | journal = Nature | volume = 386 | issue = 6622 | pages = 239–46 |date=March 1997 | pmid = 9069281 | doi = 10.1038/386239a0  | bibcode = 1997Natur.386..239K | s2cid = 4345443 }}</ref> Additional information on  GABA<sub>B</sub> receptors has been reviewed elsewhere.<ref name="pmid15989503">{{cite journal | author = Enna SJ | title = GABAB receptor agonists and antagonists: pharmacological properties and therapeutic possibilities | journal = Expert Opin Investig Drugs | volume = 6 | issue = 10 | pages = 1319–25 |date=October 1997 | pmid = 15989503 | doi = 10.1517/13543784.6.10.1319 | doi-access = free }}</ref><ref name="isbn0-89603-458-5">{{cite book |author1=Bowery, N. G. |author2=Enna, S. J. | title = The GABA receptors | publisher = Humana Press | location = Totowa, NJ | year = 1997 | isbn = 0-89603-458-5 }}</ref><ref name="pmid9872317">{{cite journal |vauthors=Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B | title = GABA(B)-receptor subtypes assemble into functional heteromeric complexes | journal = Nature | volume = 396 | issue = 6712 | pages = 683–7 |date=December 1998 | pmid = 9872317 | doi = 10.1038/25360  | bibcode = 1998Natur.396..683K | s2cid = 4421681 }}</ref><ref name="pmid9844003">{{cite journal |vauthors=Kaupmann K, Schuler V, Mosbacher J, Bischoff S, Bittiger H, Heid J, Froestl W, Leonhard S, Pfaff T, Karschin A, Bettler B | title = Human γ-aminobutyric acid type B receptors are differentially expressed and regulate inwardly rectifying K+ channels | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 25 | pages = 14991–6 |date=December 1998 | pmid = 9844003 | pmc = 24563 | doi = 10.1073/pnas.95.25.14991 | bibcode = 1998PNAS...9514991K | doi-access = free }}</ref><ref name="pmid10498952">{{cite journal |vauthors=Marshall FH, Jones KA, Kaupmann K, Bettler B | title = GABA receptors - the first 7TM heterodimers | journal = Trends Pharmacol. Sci. | volume = 20 | issue = 10 | pages = 396–9 |date=October 1999 | pmid = 10498952 | doi = 10.1016/S0165-6147(99)01383-8  }}</ref><ref name="pmid10917635">{{cite journal |vauthors=Marshall FH, White J, Main M, Green A, Wise A | title = GABA(B) receptors function as heterodimers | journal = Biochem. Soc. Trans. | volume = 27 | issue = 4 | pages = 530–5 |date=August 1999 | pmid = 10917635 | doi = 10.1042/bst0270530 }}</ref><ref name="pmid10604925">{{cite journal |vauthors=Bowery NG, Enna SJ | title = gamma-aminobutyric acid(B) receptors: first of the functional metabotropic heterodimers | journal = J. Pharmacol. Exp. Ther. | volume = 292 | issue = 1 | pages = 2–7 |date=January 2000 | pmid = 10604925 | url = http://jpet.aspetjournals.org/cgi/content/full/292/1/2 }}</ref><ref name="isbn3-540-67616-3">{{cite book | author = Enna SJ | editor = Möhler H | title = Pharmacology of GABA and Glycine Neurotransmission |series=Handbook of Experimental Pharmacology |volume=150 | publisher = Springer | location = Berlin | year = 2001 | pages = 329–342 | chapter = GABAB receptor signaling pathways | isbn = 3-540-67616-3 }}</ref>