Lack of a high affinity uptake system for the GABA agonists THIP and isoguvacine in neurons and astrocytes cultured from mouse brain.
The possibility that the GABA-receptor agonists isoguvacine and THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) might be taken up into brain cells via the high affinity GABA transport system was tested by incubation of cultured neurons and astrocytes in media containing either [(3)H]GABA, [(3)H]isoguvacine or [(3)H]THIP at different concentrations. While GABA was actively taken up into both cell types via high affinity transport mechanisms, no high affinity transport could be demonstrated for isoguvacine or THIP. Both compounds did, however, penetrate into the cells. It is concluded that isoguvacine and THIP interact with the high affinity GABA-carrier neither in neurons nor in astrocytes.
Schousboe
A
A
Department of Biochemistry A, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Larsson
O M
OM
Krogsgaard-Larsen
P
P