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)

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed prior to 1980 appear to act on sodium channels. gamma-amino butyric acid type A (GABAA) receptors (GABARs) or calcium channels. Benzodiazepines and barbiturates enhance GABAR-mediated inhibition. Phenytion, carbamazepine and possibly sodium valproate decrease high-frequency repetitive firing of action potentials by enhancing sodium channel inactivation. Ethosuximide and sodium valproate reduce a low threshold (T-type) calcium channel current. The mechanisms of action of the new AEDs are not fully established. Gabapentin binds to a high affinity site on neuronal membranes in a restricted regional distribution of the central nervous system. This binding site may be related to a possible active transport process of gabapentin into neurons; however, this has not been proven and the mechanism of action of gabapentin remains uncertain. Lamotrigine decreases sustained high-frequency repetitive firing of voltage-dependent sodium actin potentials that may result in a preferential decreased release of presynaptic glutamate. Oxcarbazepine's mechanism of action is not known; however, its similarity in structure and clinical efficacy to that of carbamazepine suggests that its mechanism of action may involve inhibition of sustained high-frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin irreversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underlie the clinical efficacy of vigabatrin. The potential mechanistic bases for rational polypharmacy are reviewed.
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PMID:Is there a mechanistic basis for rational polypharmacy? 929 30

We have recently suggested that platelets could be used as a model for neuronal receptors. In this paper we have investigated gamma-aminobutyric acid (GABA) metabolism and GABA receptors in platelets and in cultured neurons to see whether platelets' GABA mimics neuronal GABA receptor activities. We used the ELISA technique for detecting the GABA concentration in platelet rich plasma and cultured neurons. The functional effects of GABA and its receptor ligands on platelets were determined using an aggregometer. We found that the GABA concentration is 30% lower in platelets than in neurons and in both preparations GABA was metabolized by GABA transaminase (GABA-T). GABA potentiated calcium dependent platelet aggregation with a higher value in washed platelets suspension (WPS) then in platelet rich plasma (PRP). This effect was inhibited by benzodiazepines, calcium channel blockers and the selective phosphoinositide 3-kinase antagonist Wortmannin. GABA neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. We concluded that platelets could be further developed to be used as a peripheral model to study neuronal GABAergic function and its abnormality in diseases such as epilepsy and schizophrenia. Furthermore our results indicated that PI3-kinase is involved in calcium dependent GABA induced platelet aggregation as this synergistic effect is inhibited by Wortmannin in dose dependent manner.
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PMID:Investigating GABA and its function in platelets as compared to neurons. 1963 96