TY - JOUR
T1 - [3H] γ-aminobutyric acid transport in rat substantia nigra pars reticulata synaptosomes
T2 - Pharmacological characterization and phorbol ester-induced inhibition
AU - Bahena-Trujillo, Ricardo
AU - Arias-Montaño, José Antonio
PY - 1999/10/22
Y1 - 1999/10/22
N2 - In synaptosomes from rat substantia nigra pars reticulata, [3H] γ-aminobutyric acid (GABA) uptake was inhibited by GABA, (±)-nipecotic acid, β-alanine and SKF 89976-A. Inhibition was concentration-dependent and monophasic, with IC50 values that agree with those reported for the cloned rat GABA transporter GAT-1. [3H]GABA uptake was modestly, but significantly, reduced (21±3% inhibition) by 100 nM phorbol 12-tetradecanoyl-13-acetate (TPA), an activator of protein kinase C (PKC). The inhibitory action of TPA was reversed by the PKC inhibitor staurosporine (100 nM). Saturation analysis revealed that TPA reduced the maximum capacity of transport with no change in the affinity for GABA. [3H]GABA uptake was unaffected by either forskolin (10 μM) or 8-bromo-cAMP (500 μM). These results indicate that SNr GABAergic afferents express the GAT-1 transporter whose activity can be regulated by a PKC-mediated mechanism. Copyright (C) 1999 Elsevier Science Ireland Ltd.
AB - In synaptosomes from rat substantia nigra pars reticulata, [3H] γ-aminobutyric acid (GABA) uptake was inhibited by GABA, (±)-nipecotic acid, β-alanine and SKF 89976-A. Inhibition was concentration-dependent and monophasic, with IC50 values that agree with those reported for the cloned rat GABA transporter GAT-1. [3H]GABA uptake was modestly, but significantly, reduced (21±3% inhibition) by 100 nM phorbol 12-tetradecanoyl-13-acetate (TPA), an activator of protein kinase C (PKC). The inhibitory action of TPA was reversed by the PKC inhibitor staurosporine (100 nM). Saturation analysis revealed that TPA reduced the maximum capacity of transport with no change in the affinity for GABA. [3H]GABA uptake was unaffected by either forskolin (10 μM) or 8-bromo-cAMP (500 μM). These results indicate that SNr GABAergic afferents express the GAT-1 transporter whose activity can be regulated by a PKC-mediated mechanism. Copyright (C) 1999 Elsevier Science Ireland Ltd.
KW - Basal ganglia
KW - GAT-1
KW - Substantia nigra
KW - γ-Aminobutyric acid
KW - γ-Aminobutyric acid uptake
UR - http://www.scopus.com/inward/record.url?scp=0032589557&partnerID=8YFLogxK
U2 - 10.1016/S0304-3940(99)00692-8
DO - 10.1016/S0304-3940(99)00692-8
M3 - Artículo
C2 - 10553952
AN - SCOPUS:0032589557
SN - 0304-3940
VL - 274
SP - 119
EP - 122
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -