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)

A coupled peroxidation technique for localization of monoamine oxidase (MAO-A and MAO-B), applied to post-mortem fixed tissue of the locus coeruleus of the Mongolian gerbil is demonstrated. Tyramine hydrochloride, beta-phenylethylamine and 5-hydroxytryptamine creatinine sulphate were used as substrates, 1-deprenyl and clorgyline served as specific inhibitors. All three substrates stained the neurons of locus coeruleus in the absence of inhibitor. In the presence of 1-deprenyl, tyramine hydrochloride and 5-hydroxytryptamine creatinine sulphate were metabolized, whereas in the presence of clorgyline no reaction with either substrate could be observed. Immunocytochemical staining of tyrosine hydroxylase (TH) was employed as comparison.
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PMID:Histochemistry of MAO-A and MAO-B in the locus coeruleus of the Mongolian gerbil. 368 Dec 91

1. Reserpine in vitro (10(-5)M) caused a profound inhibition (>85%) of the formation of both (14)C-catecholamine ((14)C-CA) and (14)C-dihydroxyphenylalanine ((14)C-DOPA) (in the presence of the amino acid decarboxylase inhibitor brocresine) from (14)C-tyrosine in guinea-pig vas deferens. The magnitude of the inhibition was similar for both (14)C-CA and (14)C-DOPA suggesting that the inhibition occurred primarily at the tyrosine hydroxylase step.2. One hour after in vivo treatment with reserpine (1 mg/kg) when tissue stores of noradrenaline (NA) were depleted by 50%, there was a significant inhibition of the formation of (14)C-DOPA. Twenty-four hours after such treatment, when endogenous NA could no longer be detected, synthesis of (14)C-DOPA was indistinguishable from untreated controls. However a 45% inhibition of (14)C-DOPA synthesis from (14)C-tyrosine could be produced in tissues which had been depleted of NA for 24 h or 48 h by the addition of reserpine, 10(-5)M, to the incubation medium.3. Addition of pteridine cofactor, 2-amino-6,7,-dimethyl-4-hydroxy-5,6,7,8-tetrahydropteridine, to the incubation medium in a concentration of 5 x 10(-3)M enhanced the formation of both (14)C-CA and (14)C-DOPA from (14)C-tyrosine in guinea-pig vas deferens. In 52 mM KCl Krebs-Henseleit medium (14)C-CA formation increased from 2.58+/-0.20 (nmol/g)/h to 6.35+/-0.47 (nmol/g)/h whilst (14)C-DOPA formation increased from 5.04+/-0.88 (nmol/g)/h to 11.29+/-0.59 (nmol/g)/h.4. Pteridine cofactor (5 x 10(-3)M) did not reverse the inhibition of (14)C-DOPA formation seen with reserpine (10(-5)M) in previously untreated tissues or in vasa deferentia from animals pretreated with reserpine 1 mg/kg for 24 hours. However, the inhibition did disappear in the presence of pteridine cofactor when treatment with reserpine was prolonged to 48 h and included two doses of reserpine of 2 mg/kg.5. Tyramine (5.8 x 10(-5)M) and bretylium (10(-5)M) in vitro inhibited the formation of (14)C-CA and (14)C-DOPA from (14)C-tyrosine to the same extent in guinea-pig vas deferens again indicating that their major site of action is on tyrosine hydroxylase. The inhibitory effects were reversed by pteridine cofactor.6. Synthesis of (14)C-NA from (14)C-tyrosine in calf splenic nerve was not increased by incubating the tissue in 52 mM KCl-Krebs-Henseleit solution.
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PMID:Effect of drugs on the synthesis of noradrenaline in guinea-pig vas deferens. 465 68

Slices of striatal tissue obtained from saline-injected rats were incubated with 3H-phenylalanine in the presence of pargyline. This resulted in the formation of 3H-m-tyramine, 3H-p-tyramine, and 3H-phenylethylamine. Pretreatment of the rats with alpha-methyl-p-tyrosine reduced the formation of 3H-m-tyramine and 3H-p-tyramine, but enhanced the formation of 3H-phenylethylamine. After incubation of striatal tissue obtained from saline-injected rats with 3H-ptyrosine, only 3H-p-tyramine was produced. In this case, alpha-methyl-p-tyrosine pretreatment enhanced 3H-p-tyramine formation. Striatal slices incubated with 3H-m-tyramine or 3H-p-tyramine did not yield any significant quantity of 3H-phenylethylamine; nor was 14C-phenylethylamine converted to 14C-m-tyramine or 14C-p-tyramine. Pretreatment of the rats with the monoamine oxidase inhibitor pargyline did not appreciably affect these findings. After incubation with 3H-dopamine very small quantities of 3H-m-tyramine and 3H-p-tyramine were formed, the ratio between them being 7:1. It is concluded that the major biosynthetic route for m-tyramine formation in the rat striatum is by hydroxylation of phenylalanine, probably by tyrosine hydroxylase to m-tyrosine, followed by decarboxylation, probably by L-aromatic amino acid decarboxylase, to m-tyramine. para-Tyramine is formed by decarboxylation of p-tyrosine, and phenylethylamine similarly by decarboxylation of phenylalanine.
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PMID:The biosynthesis of p-tyramine, m-tyramine, and beta-phenylethylamine by rat striatal slices. 663 7

Dopamine is formed form L-tyrosine by tyrosine hydroxylase and aromatic L-amino acid decarboxylase. In addition to this pathway, however, the formation of catecholamines, including dopamine, from trace amines such as tyramine by hepatic microsomes has been demonstrated. In this study, we investigated the formation of dopamine from trace amines, using human hepatic microsomes and human cytochrome P450 (CYP) isoforms expressed in yeast. Among the 11 isoforms of human CYP expressed in yeast, CYP2D6 was the only isoform exhibiting strong ability to convert p-tyramine and m-tyramine to dopamine. In studies with human hepatic microsomes, the hydroxylation of tyramine to dopamine was inhibited by bufuralol, a typical substrate for CYP2D isoforms, and anti-CYP2D1 antiserum. This is the first report showing that CYP2D is capable of converting tyramine to dopamine. The Km values of CYP2D6, expressed in yeast, for p-tyramine and m-tyramine were 190.1 +/- 19.5 microM and 58.2 +/- 13.8 microM, respectively. Tyramine is an endogenous compound which exists in the brain as a trace amine but is also an exogenous compound which is found in foods such as cheese and wine. Our results suggest that dopamine is formed from endogenous and/or exogenous tyramine by this CYP2D isoform.
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PMID:Dopamine formation from tyramine by CYP2D6. 973 Dec 23

The balance between norepinephrine (NE) synthesis, release, and reuptake is disrupted after acute myocardial infarction, resulting in elevated extracellular NE. Stimulation of sympathetic neurons in vitro increases NE synthesis and the synthetic enzyme tyrosine hydroxylase (TH) to a greater extent than it increases NE reuptake and the NE transporter (NET), which removes NE from the extracellular space. We used TGR(ASrAOGEN) transgenic rats, which lack postinfarct sympathetic hyperactivity, to test the hypothesis that increased cardiac sympathetic nerve activity accounts for the imbalance in TH and NET expression in these neurons after myocardial infarction. TH and NET mRNA levels were identical in the stellate ganglia of unoperated TGR(ASrAOGEN) rats compared with Sprague Dawley (SD) controls, but the threefold increase in TH and twofold increase in NET mRNA seen in the stellate ganglia of SD rats 1 wk after ischemia-reperfusion was absent in TGR(ASrAOGEN) rats. Similarly, the increase in TH and NET protein observed in the base of the SD ventricle was absent in the base of the TGR (ASrAOGEN) ventricle. Neuronal TH content was depleted in the left ventricle of both genotypes, whereas NET was unchanged. Basal heart rate and cardiac function were similar in both genotypes, but TGR(ASrAOGEN) hearts were more sensitive to the beta-agonist dobutamine. Tyramine-induced release of endogenous NE generated similar changes in ventricular pressure and contractility in both genotypes, but postinfarct relaxation was enhanced in TGR(ASrAOGEN) hearts. These data support the hypothesis that postinfarct sympathetic hyperactivity is the major stimulus increasing TH and NET expression in cardiac neurons.
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PMID:Postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter. 1795 70