UNASSIGNED: The ability to modulate the synaptic GABA levels has been demonstrated by using the clinically effective and selective @entity25177 inhibitor tiagabine [(R)-N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid]. N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-hydroxy-4-(methylamino)-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol ( @entity68696 ) which not only inhibits @entity25177 like tiagabine but also @entity67019 has been shown to modulate extrasynaptic GABA levels. The simultaneous inhibition of synaptic and extrasynaptic GABA transporters using tiagabine and @entity68696 , respectively has been demonstrated to exert a synergistic anticonvulsant effect in several @entity410 models in @entity19 . The pharmacological profile of these and similar compounds has been thoroughly investigated in in vitro systems, comparing the GAT subtype selectivity with the ability to inhibit GABA uptake in primary cultures of neurons and astrocytes. However, an exact explanation has not yet been found. In the present study, the ability of @entity28788 to form homo and/or heterodimers was investigated as well as to which membrane micro environment the @entity28788 reside. To investigate dimerization of @entity28788 , fusion proteins of @entity28788 tagged with either yellow fluorescent protein or cerulean fluorescent protein were made and fluorescence resonance energy transfer (FRET) was measured. It was found that @entity28788 form both homo- and hetero-dimers in N2A and HEK-293 cells. Microdomain localization of @entity28788 as investigated by detergent resistant membrane fractions after treatment of tissue with @entity36368 or Triton X-100 revealed that @entity67019 and @entity25177 mostly localize to non-membrane rafts independent of the detergent used. However, @entity25178 localizes to membrane rafts when using @entity36368 . Taken together, these results suggest that the observed hetero dimerization of @entity28788 in the FRET study is unlikely to have functional implications since the @entity28788 are located to very different cellular compartments and cell types.

The Subcellular Localization of GABA Transporters and Its Implication for XXXX Management.

@entity410 :: ('MESH:D012640', 'Disease') :: ['seizure'] @entity25177 :: ('6529', 'Gene') :: ['GAT1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity28788 :: ('352954', 'Gene') :: ['GATs'] @entity25178 :: ('6540', 'Gene') :: ['GAT3'] @entity67019 :: ('6539', 'Gene') :: ['BGT1'] @entity36368 :: ('MESH:C033084', 'Chemical') :: ['Brij-98'] @entity68696 :: ('MESH:C510806', 'Chemical') :: ['EF1502']
@entity410 :: (MESH:D012640,Disease) :: ['Seizure']
