Use of Inhibitors of γ‐Aminobutyric Acid (GABA) Transaminase for the Estimation of GABA Turnover in Various Brain Regions of Rats: A Reevaluation of Aminooxyacetic Acid

Löscher, Wolfgang; Hönack, Dagmar; Gramer, Martina

doi:10.1111/j.1471-4159.1989.tb09239.x

Cited by 60 publications

(34 citation statements)

References 42 publications

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“…When AOAA is given, GABA continues to be synthesized and released but is not degraded. Thus, comparing the rate of increase in GABA following AOAA (accumulation rate) in Ovx, Ovx + EB, and Ovx + EB + P-treated rats provides a relative measure of GABA activity or turnover after these treatments [14]. …”

Section: Resultsmentioning

confidence: 99%

“…The rate of accumulation (turnover) gives a measurement of GABA activity. Turnover rates are relative, but are valid indicators of activity when assumptions of the technique are satisfied and appropriate between-group comparisons are made [14]. Previous studies show that accumulation rates in preoptic-hypothalamic nuclei at this dose are selective and linear up to 1 h post-AOAA [5, 14].…”

Section: Methodsmentioning

confidence: 99%

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GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

Luine

Hoffman

et al. 1999

Neuroendocrinology

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The role of GABAergic neurons in activating female sexual behavior and possible mechanisms for GABAergic effects on behavior were examined in female rats. First, effects of the ovarian hormones estrogen and progesterone (P), at doses which promote lordosis, on levels and turnover/activity of GABA, were examined in brain areas which regulate lordosis. Utilizing AOAA, an inhibitor of GABA degradation, the accumulation rate of GABA (turnover/activity) was assessed in ovariectomized (Ovx), Ovx + estrogen and Ovx + estrogen + P-treated rats. Estradiol increased GABA accumulation rates in the arcuate-median eminence and in the area dorsal to and surrounding the VMN (VMN-S). P administration following estrogen priming enhanced GABA turnover in the medial preoptic area (mPOA) and further increased turnover in the VMN-S while GABA turnover decreased in the dorsomedial nucleus. No effects of hormones were noted in the VMN itself or in the dorsal midbrain central gray. Reverse dialysis of the GABA_A antagonist bicuculline into the basomedial hypothalamus was associated with a time-dependent inhibition of lordosis and a 300% increase in 5-HT release in the basomedial hypothalamus as measured by in vivo dialysis. These results provide additional evidence that GABAergic neurons mediate the physiological regulation of female sexual behavior and suggest that such mediation may involve an interaction with 5-HT containing neurons.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

Luine

Hoffman

et al. 1999

Neuroendocrinology

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“…In order to assess the functional activity of a population of neurons, we have used a neurochemical estimate of neurotransmitter turnover [see 17, 27]. Lactating rats with pups had a significantly higher rate of GABA turnover in the VLPO than the lactating rats without pups, suggesting that GABA turnover was stimulated by the acute suckling stimulus.…”

Section: Discussionmentioning

confidence: 99%

Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat

Kornblatt¹,

Grattan²

2001

Neuroendocrinology

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γ-Aminobutyric acid (GABA) neurons terminating in the hypothalamus have been implicated in the neuroendocrine regulation of reproductive hormones, particularly luteinizing hormone (LH) and prolactin. The aim of this study was to examine whether GABAergic neuronal activity in the hypothalamus was modified during lactation, and whether any observed changes correlated with changes in secretion of these hormones. Animals were divided into three experimental groups: diestrous controls, lactating with pups present (with pups), and lactating with pups removed for 4 h (without pups). Animals were decapitated either without treatment, or 60 min after inhibition of GABA degradation by aminooxyacetic acid (AOAA) (100 mg/kg, i.p.). The rate of GABA accumulation in the tissue after AOAA is a measure of GABA turnover. GABA turnover was estimated in 13 microdissected brain regions, and serum prolactin and LH measured by radioimmunoassay. Suckling was associated with significantly increased prolactin and significantly decreased LH compared with diestrous rats. In lactating rats with pups, GABA turnover was significantly increased in the cingulate cortex compared with diestrous rats. GABA turnover was significantly increased in the ventrolateral preoptic nucleus of lactating rats with pups compared with diestrous rats or lactating rats without pups. There was significantly lower GABA turnover in the anterior hypothalamic area, ventromedial and dorsomedial hypothalamic nuclei in lactating rats without pups compared with diestrous rats. There were no significant changes in other brain regions examined. The results demonstrate that activity of GABAergic neurons in specific parts of the hypothalamus and cerebral cortex is altered during lactation.

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“…When two values are given, the first valuc is from Casu and Gale (198 I ) and the second from Loscher et al (1989).…”

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confidence: 99%

“…' TCA cycle fluxes (in nanomoles per minute per milligram of protein) for rat brain regions are calculated from local glucose utilization rates as measured with 2-deoxyglucose (Sokoloff et al, 1977) by assuming that 85% ofglucose enters the TCA cycle as acetyl-CoA (Patel et al, 1970) and by using the value for protein content of each brain region from Loscher et al (1989). ble l), indicating that GAD operates at a small fraction of its maximal catalytic capacity.…”

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confidence: 99%

Regulation of γ‐Aminobutyric Acid Synthesis in the Brain

Martin

Rimvall

1993

Journal of Neurochemistry

562

363

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y-Aminobutyric acid (GABA) is synthesized in brain in at least two compartments, commonly called the transmitter and metabolic compartments, and because regulatory processes must serve the physiologic function of each compartment, the regulation of GABA synthesis presents a complex problem. Brain contains at least two molecular forms ofglutamate decarboxylase (GAD), the principal synthetic enzyme for GABA. Two forms, termed GAD65 and GAD6,, are the products of two genes and differ in sequence, molecular weight, interaction with the cofactor, pyridoxal 5'-phosphate (pyridoxal-P), and level of expression among brain regions. GAD,, appears to be localized in nerve terminals to a greater degree than GAD,,, which appears to be more uniformly distributed throughout the cell. The interaction of GAD with pyridoxal-P is a major factor in the short-term regulation of GAD activity. At least 50%of GAD is present in brain as apoenzyme (GAD without bound cofactor; apoGAD), which serves as a reservoir of inactive GAD that can be drawn on when additional GABA synthesis is needed. A substantial majority of apoGAD in brain is accounted for by GAD,,, but GAD,, also contnbUtes to the pool of apoGAD. The apparent localization of GAD,, in nerve terminals and the large reserve of apo-GAD,, suggest that GAD,, is specialized to respond to short-term changes in demand for transmitter GABA. The levels of apoGAD and the holoenzyme ofGAD (holoGAD) are controlled by a cycle of reactions that is regulated by physiologically relevant concentrations of ATP and other polyanions and by inorganic phosphate, and it appears possible that GAD activity is linked to neuronal activity through energy metabolism. GAD is not saturated by glutamate in synaptosomes or cortical slices, but there is no evidence that GABA synthesis in vivo is regulated physiologically by the availability of glutamate. GABA competitively inhibits GAD and converts holo-to apoGAD, but it is not clear if intracellular GABA levels are high enough to regulate GAD. There is no evidence of short-term regulation by second messengers. The syntheses of GAD,, and GAD,, proteins are regulated separately. GAD,, regulation is complex: it not only is present as apoGAD,,, but the expression of GAD,, protein is regulated by two mechanisms: (a) by control of mRNA levels and (b) at the level of translation or protein stability. The latter mechanism appears to be mediated by intracellular GABA levels. Key Words: y-Aminobutyric acid synthesis regulation-Glutamate decarboxylase-Pyridoxal 5'-phosphate. Martin D. L. and Rimvall K. Regulation of y-aminobutync acid synthesis in the brain. J . Neurochern. 60, 395-407 ( 1993). y-Aminobutyric acid (GABA) synthesis is a highly regulated process in brain. Many studies with synaptosomes and brain slices and in vivo have shown that GABA synthesis can be stimulated or suppressed by physiological or pharmacological manipulations (see, e.g., Moroni et al.,

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Use of Inhibitors of γ‐Aminobutyric Acid (GABA) Transaminase for the Estimation of GABA Turnover in Various Brain Regions of Rats: A Reevaluation of Aminooxyacetic Acid

Cited by 60 publications

References 42 publications

GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat

Regulation of γ‐Aminobutyric Acid Synthesis in the Brain

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