Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems.
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PMID:Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. 0 34

Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.
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PMID:Determination of amino acids and monoamine neurotransmitters in caudate nucleus of seizure-resistant and seizure-prone BALB/c mice. 768 Nov

Lamotrigine (LTG), an anticonvulsive drug, was tested for its effects on striatal content of DA and its metabolites, DOPAC and HVA, in audiogenic seizure-resistant (ER) and audiogenic seizure-prone (EP) lines of Balb/c mice. A single dose of LTG (20 mg/kg) prevented audiogenic seizures in seizure-prone mice, while reducing substantially the striatal content of the DA metabolite, DOPAC (to less than 50% of saline-injected controls) in both seizure-resistant and seizure-prone mice. LTG administration also resulted in significant reduction of striatal content of HVA. The in situ activity of tyrosine hydroxylase (TH) in extracts of striatum was significantly reduced by LTG administration in both ER and EP mice. These data show that DA synthesis in the striatum of mice is substantially reduced by LTG administration.
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PMID:Lamotrigine inhibits the in situ activity of tyrosine hydroxylase in striatum of audiogenic seizure-prone and audiogenic seizure-resistant Balb/c mice. 941 65

The genetically epilepsy-prone rat (GEPR) is a model of generalized tonic/clonic epilepsy, and has functional noradrenergic deficiencies that act as partial determinants for the seizure predisposition and expression. The present study investigated the effect of repeated seizure experiences by acoustic stimulation (110 dB, 10 times) on the immunoreactivities of tyrosine hydroxylase (TH), a rate-determining enzyme in the synthesis of norepinephrine, in brain regions of GEPRs. TH immunoreactivity in locus coeruleus, the major noradrenergic nucleus in brain, was lower in GEPRs than control Sprague-Dawley rats. It was also decreased in several regions including inferior colliculus of GEPRs. Repeated experiences of audiogenic seizures further decreased TH immunoreactivities in locus coeruleus and inferior colliculus of GEPRs. The results from the present study suggest that the lower immunoreactivities of TH in locus coeruleus and inferior colliculus contribute, at least in part, to the noradrenergic deficits in GEPRs, and repeated seizure experiences further intensified these noradrenergic deficits, which may be related to the altered seizure expression by repetitive audiogenic seizure in GEPRs.
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PMID:Effect of repeated seizure experiences on tyrosine hydroxylase immunoreactivities in the brain of genetically epilepsy-prone rats. 1117 42