Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.
Pol J Pharmacol Pharm
PMID:The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. 130 60

gamma-Aminobutyric acid (GABA) belongs to main inhibitory neurotransmitters in the central nervous system and activates three types of specific receptors--GABAA, GABAB i GABAC. At present, little is known about GABAC-mediated events. GABAB receptors are metabotropic, whilst stimulation of ionotropic GABAA receptors results in opening the chloride channel, followed by influx of chloride ions and hyperpolarization. The GABAA receptor possesses also binding sites for benzodiazepines and barbiturates which, via these sites, enhance GABAA-mediated events. Another antiepileptic drug potentiating GABA-ergic inhibition is valproate, which increases synthesis of GABA and reduces its metabolism. Among new antiepileptic drugs associated with the GABA-ergic system are tiagabine, vigabatrin, and to a certain degree--gabapentin. Tiagabine blocks neuronal and glial uptake of GABA whilst vigabatrin increases the synaptic concentration of GABA by inhibition of GABA aminotransferase. Gabapentin, probably through the activation of glutamic acid decarboxylase, leads to the increase in synaptic GABA. However, this antiepileptic drugs is also binds to specific sites within voltage-dependent calcium channels, which results in the reduced intraneuronal concentration of calcium ions. Presumably, tiagabine and vigabatrin possess only one mechanism of action, associated with the increased GABA-ergic inhibition. Although topiramate and felbamate were shown to enhance GABA-mediated events, they have additional mechanisms of action, including blockade of voltage-dependent sodium channels and inhibition of glutamatergic neurotransmission.
Neurol Neurochir Pol 2000
PMID:[GABA-ergic system and antiepileptic drugs]. 1076 41

gamma-Aminobutyric acid (GABA) belongs to the main inhibitory neurotransmitters in the central nervous system and activates three types of specific receptors--GABAA, GABAB i GABAC. At present, little is known about GABAC-mediated events. GABAB receptors are metabotropic, whilst stimulation of ionotropic GABAA receptors results in opening the chloride channel, followed by influx of chloride ions and hyperpolarization. The GABAA receptor possesses also binding sites for benzodiazepines and barbiturates which, via these sites, enhance GABAA-mediated events. Another antiepileptic drug potentiating GABA-ergic inhibition is valproate, which increases synthesis of GABA and reduces its metabolism. Among new antiepileptic drugs associated with the GABA-ergic system are tiagabine, vigabatrin, and to a certain degree--gabapentin. Tiagabine blocks neuronal and glial uptake of GABA whilst vigabatrin increases the synaptic concentration of GABA by inhibition of GABA aminotransferase. Gabapentin, probably through the activation of glutamic acid decarboxylase, leads to the increase in synaptic GABA. However, this antiepileptic drug also binds to specific sites within voltage-dependent calcium channels, which results in reduced intraneuronal concentration of calcium ions. Presumably, tiagabine and vigabatrin possess only one mechanism of action, associated with increased GABA-ergic inhibition. Although topiramate and felbamate were shown to enhance GABA-mediated events, they have additional mechanisms of action, including blockade of voltage-dependent sodium channels and inhibition of glutamatergic neurotransmission.
Neurol Neurochir Pol
PMID:[GABA-ergic system and antiepileptic drugs]. 1079 Oct 39

One of the hypotheses in amyotrophic lateral sclerosis (ALS) indicates on excitatory amino acids as the cause of neuronal death. Changes in their concentration in the tissues and body fluids may be the consequence of a defect in their transport, as well as abnormal activities of glutamate metabolizing enzymes. Abnormal synthesis/degradation of these enzymes and/or influence of activators/inhibitors should be taken into account. The activity of enzymes of glutamate metabolism of rat spinal cord in vitro in the presence of serum and cerebrospinal fluid (CSF) of 20 patients with ALS and 20 healthy controls was tested. In the presence of serum of the ALS patients glutaminase was significantly stimulated, instead of being inhibited; the inhibition of GABA aminotransferase, glutamate decaboxylase and aspartate aminotransferase was less evident than in the controls, glutamate dehydrogenase lost its activity more than in control conditions, the inhibition of glutamine synthetase was comparable to that when normal serum was applied. The activity of the enzymes in the presence of CSF of ALS patients was generally similar to that of normal CSF, except of glutaminase which was stimulated and GABA aminotransferase, which was inhibited stronger than in the presence of normal CSF. This study indicates, that changes in glutamate concentration in tissues and body fluids in ALS may be caused, at least partly, by abnormalities in the activity of glutamate metabolism enzymes, which are in turn induced by neurotoxic agents present in body fluids of ALS patients.
Neurol Neurochir Pol 2001
PMID:[Neurotoxic activity of serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients against some enzymes of glutamate metabolism]. 1173 83

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well-tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring significant qualitive change in the possibilities of pharmacotherapy.
Neurol Neurochir Pol 2000
PMID:[Gabaergic hypothesis of epilepsy and clinical experience: controversial actions of the new generation gabamimetic antiepileptic drugs]. 1178 May 94