| First Author | Sigel E | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 44 | Pages | 18150-5 |
| PubMed ID | 22025726 | Mgi Jnum | J:180249 |
| Mgi Id | MGI:5305900 | Doi | 10.1073/pnas.1113444108 |
| Citation | Sigel E, et al. (2011) The major central endocannabinoid directly acts at GABA(A) receptors. Proc Natl Acad Sci U S A 108(44):18150-5 |
| abstractText | GABA(A) receptors are the major ionotropic inhibitory neurotransmitter receptors. The endocannabinoid system is a lipid signaling network that modulates different brain functions. Here we show a direct molecular interaction between the two systems. The endocannabinoid 2-arachidonoyl glycerol (2-AG) potentiates GABA(A) receptors at low concentrations of GABA. Two residues of the receptor located in the transmembrane segment M4 of beta(2) confer 2-AG binding. 2-AG acts in a superadditive fashion with the neurosteroid 3alpha, 21-dihydroxy-5alpha-pregnan-20-one (THDOC) and modulates delta-subunit-containing receptors, known to be located extrasynaptically and to respond to neurosteroids. 2-AG inhibits motility in CB(1)/CB(2) cannabinoid receptor double-KO, whereas beta(2)-KO mice show hypermotility. The identification of a functional binding site for 2-AG in the GABA(A) receptor may have far-reaching consequences for the study of locomotion and sedation. |
