TY - JOUR
T1 - In vivo action of enzyme-activated irreversible inhibitors of glutamic acid decarboxylase and γ-aminobutyric acid transaminase in retina vs. brain
AU - Cubells, J. F.
AU - Blanchard, J. S.
AU - Smith, D. M.
AU - Makman, M. H.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1986
Y1 - 1986
N2 - The effects of low s.c. doses of γ-acetylenic γ-aminobutyric acid (GAG) on glutamic acid decarboxylase (GAD) and γ-aminobutyric acid transaminase (GABA-T) activities, as well as of γ-vinyl GABA (GVG) and gabaculine on GABA-T activities, were examined using preparations from retina and several other regions of rat central nervous system (CNS). GAG, in doses of 5 to 50 mg/kg, inactivated retinal GAD to a significantly greater degree than GAD from any other CNS region studied. Retinal GABA-T activities were also differentially inactivated by 1 to 50 mg/kg of GAG, 50 mg/kg of GVG, or 1 and 5 mg/kg of gabaculine. GAG, in doses of 25 and 50 mg/kg, more completely inactivated GAD and GABA-T in frontal cortex than in other brain regions. Frontal cortical GABA-T was not differentially inactivated by 10 and 50 mg/kg of GVG or 1 and 5 mg/kg of gabaculine. The effects of GAG on retinal GABA enzymes were long-lasting and not reversed by dialysis. The GAD and GABA-T activities from 1:1 mixes of control and GAG-treated retinal preparations were comparable to the means of the GAG-treated and control activities. The effects documented in this study, therefore, probably reflect irreversible in vivo changes. After peripheral administration, GAG, GVG and gabaculine might reach higher levels in the retina than in the brain. Alternatively, the differential effects of these compounds might be due to the relative proportions of catalytically active GABA enzymes in different CNS regions. On the basis of the foregoing results, the retina might be a particularly suitable region of the CNS for enzyme-activated irreversible inhibitors to label catalytically active enzymes of GABA metabolism.
AB - The effects of low s.c. doses of γ-acetylenic γ-aminobutyric acid (GAG) on glutamic acid decarboxylase (GAD) and γ-aminobutyric acid transaminase (GABA-T) activities, as well as of γ-vinyl GABA (GVG) and gabaculine on GABA-T activities, were examined using preparations from retina and several other regions of rat central nervous system (CNS). GAG, in doses of 5 to 50 mg/kg, inactivated retinal GAD to a significantly greater degree than GAD from any other CNS region studied. Retinal GABA-T activities were also differentially inactivated by 1 to 50 mg/kg of GAG, 50 mg/kg of GVG, or 1 and 5 mg/kg of gabaculine. GAG, in doses of 25 and 50 mg/kg, more completely inactivated GAD and GABA-T in frontal cortex than in other brain regions. Frontal cortical GABA-T was not differentially inactivated by 10 and 50 mg/kg of GVG or 1 and 5 mg/kg of gabaculine. The effects of GAG on retinal GABA enzymes were long-lasting and not reversed by dialysis. The GAD and GABA-T activities from 1:1 mixes of control and GAG-treated retinal preparations were comparable to the means of the GAG-treated and control activities. The effects documented in this study, therefore, probably reflect irreversible in vivo changes. After peripheral administration, GAG, GVG and gabaculine might reach higher levels in the retina than in the brain. Alternatively, the differential effects of these compounds might be due to the relative proportions of catalytically active GABA enzymes in different CNS regions. On the basis of the foregoing results, the retina might be a particularly suitable region of the CNS for enzyme-activated irreversible inhibitors to label catalytically active enzymes of GABA metabolism.
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M3 - Article
C2 - 3735130
AN - SCOPUS:0022485685
SN - 0022-3565
VL - 238
SP - 508
EP - 514
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -