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

The release of endogenous dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) was measured in superfused striatal slices of the rat and the results compared with data obtained for the release of endogenous (a) DA and DOPAC in the cerebral cortex, nucleus accumbens and thalamus; (b) 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), GABA, and glutamate in the striatum; and (c) GABA, glutamate and 5-HT in the cerebral cortex. In superfused slices of all four CNS regions, there appeared to be a Ca2+-dependent, K+-stimulated release of endogenous DA. In addition, in slices of the striatum and nucleus accumbens there also appeared to be a Ca2+ -dependent, 60 mM K+ stimulated release of endogenous DOPAC. In the striatum, 16 mM Mg2+ was as effective as 2.5 mM Ca2+ in promoting the 60 mM K+-stimulated release of DOPAC. In addition, 16 mM Mg2+ appeared to function as a weak Ca2+ agonist since it also promoted the release of DA to approximately 40% of the level attained with Ca2+ in the presence of 60 mM K+. On the other hand, in the striatum, 16 mM Mg2+ inhibited the Ca2+-dependent, 60 mM K+-stimulated release of GABA and glutamate. Similar Mg2+-inhibition was observed in the cerebral cortex not only for GABA and glutamate but also for DA and 5-HT. With the use of alpha-methyl rho-tyrosine (tyrosine hydroxylase inhibitor), cocaine (uptake inhibitor) and pargyline (monoamine oxidase inhibitor), it was determined that most of the released DA and DOPAC was synthesized in the slices during the superfusion; DOPAC was not formed from DA which had been released and taken up; and DA and DOPAC were released from DA nerve terminals. In addition, the data indicate a difference in the release process between the amino acids and the monoamines from striatal slices since Mg2+ inhibited the Ca2+-dependent, K+-stimulated release of GABA and glutamate and appeared to promote the release of DA and 5-HT.
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PMID:Release of endogenous dopamine, 3,4-dihydroxyphenylacetic acid, and amino acid transmitters from rat striatal slices. 286 May 79

CSF was continuously withdrawn from the third ventricle of anesthetized rats. CSF 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid concentrations were determined every 15 min by liquid chromatography coupled with electrochemical detection. Acute tyrosine hydroxylase inhibition [with alpha-methyl-p-tyrosine (alpha-MPT)] induced an exponential decline in levels of DOPAC and HVA in CSF. The decline in DOPAC and HVA concentrations was identical in CSF and forebrain but was much slower in the striatum, suggesting that CSF metabolites of 3,4-dihydroxyphenylethylamine (dopamine) reflect whole forebrain metabolites. The decay in CSF DOPAC and HVA levels after dopamine synthesis inhibition was also used as an in vivo index of forebrain dopamine turnover after various pharmacological treatments. Haloperidol pretreatment accelerated this decay, confirming the increase in brain dopamine turnover induced by neuroleptics. After reserpine pretreatment (15 h before), alpha-MPT produced a very sharp decay in levels of DOPAC and HVA. This result indicates that the residual dopamine that cannot be stored after reserpine treatment is very rapidly renewed and metabolized. Nomifensine strongly diminished the slope of DOPAC and HVA level decreases after alpha-MPT, a result which can be explained either by a slower dopamine turnover or by the involvement of storage dopamine pools. These results exemplify the use of monitoring the decay of dopamine metabolites after alpha-MPT administration in the study of the pharmacological action of drugs on the central nervous system of the rat.
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PMID:Study of dopamine turnover by monitoring the decline of dopamine metabolites in rat CSF after alpha-methyl-p-tyrosine. 286 97

The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
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PMID:The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. 287 93

Many of the rewarding aspects of cocaine are thought to be due to the ability of this stimulant to block reuptake of monoamines. However, because of its ability also to cause transmitter release, it is difficult to examine the properties of cocaine as an uptake blocker using in vitro techniques such as tissue slices or synaptosomes. Thus, we have evaluated cocaine as a blocker of dopamine and 5-hydroxytryptamine uptake processes by determining the in vivo effect of concurrent administrations of cocaine on the neurochemical effects of methamphetamine treatments. These findings demonstrated that cocaine like 5-hydroxytryptamine uptake blockers such as citalopram, greatly attenuated or blocked decreases in striatal and cortical tryptophan hydroxylase activities and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid induced by multiple and single methamphetamine administrations. In contrast to other dopamine uptake blockers, such as amfonelic acid, cocaine did not attenuate the methamphetamine effects on striatal tyrosine hydroxylase activity and the concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid. The neurochemical findings were correlated with behavioral analyses.
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PMID:Effects of cocaine on methamphetamine-induced neurochemical changes: characterization of cocaine as a monoamine uptake blocker. 288 43

To analyze the dynamics of sympathetic input to the chicken pineal the concentrations of catecholamines, indoleamines and some of their metabolites were determined by high performance liquid chromatography with electrochemical detection (HPLC-EC) in the pineal glands of young chickens killed at different times of day. Rhythmic variations over 24 h were observed in tissue levels of dopamine (DA), 5-hydroxytryptamine (5-HT), N-acetylserotonin (NAS) and 5-hydroxyindoleacetic acid (5-HIAA), while norepinephrine (NE) concentrations exhibited no significant change. DA content peaked 2 h after onset of darkness and NAS was detectable only during the night. A bimodal pattern of 5-HT and 5-HIAA levels was observed with peak tissue levels occurring at dawn and dusk. To determine the possible differential effects of light on these biogenic amines, birds were sacrificed at midday, midnight and at midnight following a 1 h exposure to light, and their pineals processed for HPLC-EC. NE, DA and 5-HT levels were similar at midday and midnight, while 5-HIAA and NAS were elevated during the night. Midnight illumination decreased NE and NAS levels, increased 5-HT and 5-HIAA levels and had no effect on DA levels. Temporal variations in NE turnover were determined by pretreating young chickens with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, and measuring the rates of decline in NE content over 2 h at midday and midnight in birds held on light cycles and at mid-subjective day in birds held in constant darkness (DD).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamics of noradrenergic circadian input to the chicken pineal gland. 377 84

The role of the serotonin uptake carrier in the methamphetamine-induced depression of serotonin synthesis was examined. In vivo, coadministration of citalopram or chlorimipramine with methamphetamine blocked the irreversible depression of tryptophan hydroxylase activity observed in the neostriatum and cerebral cortex after repeated administration of high doses of methamphetamine. The methamphetamine-induced reduction of neostriatal serotonin and 5-hydroxyindoleacetic acid was also attenuated by the two uptake inhibitors. In contrast, neither drug antagonized the depression of neostriatal tyrosine hydroxylase activity observed after methamphetamine administration. Citalopram also blocked the reversible inhibition of tryptophan hydroxylase activity observed after the acute administration of methamphetamine. In vitro, citalopram significantly inhibited methamphetamine-induced [3H]serotonin release from neostriatal slices. The results demonstrate that inhibitors of the serotonin uptake carrier can antagonize both the in vivo and in vitro effects of methamphetamine on serotonergic neurons. Furthermore, the methamphetamine-induced depression of serotonin synthesis is dependent upon a functional serotonin uptake system.
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PMID:Role of the serotonin uptake carrier in the neurochemical response to methamphetamine: effects of citalopram and chlorimipramine. 385 54

Marked enhancement of tyrosine hydroxylase (TH) activity was observed in the rostral pons of Wistar albino rats, 3 days after a single injection of Oxotremorine. TH activity in other brain areas, and regional levels of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid were unaffected. Enhancement of TH activity did not affect length or number of REM episodes, or the amount of REM occurring in 24 hr. REM occurrence did not, thus, vary in accordance with activity of the rate-limiting enzyme for catecholamine synthesis. These data suggest that, although REM may reflect neuronal protein synthesis, REM is not part of a mechanism regulating the activity of enzymes in the pontine CA synthesis pathway.
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PMID:Enhancement of tyrosine hydroxylase activity by Oxotremorine does not affect sleep in the rat. 610 19

A single injection of melanocyte-stimulating hormone inhibitory factor (MIF-1) in a dose of 3 mg/kg IP produced no significant effect on dopamine turnover. However, a dose of 5 mg/kg increased striatal tyrosine hydroxylase activity by 25% and homovanillic acid level by 27% when compared to control values. No change in either parameter was detected in olfactory tubercles. Dopamine levels also were elevated in striatum, pons-medulla and cerebral cortex in rats receiving 5 mg/kg dose of MIF-1. In olfactory tubercles, dopamine levels were however, reduced to 71% of control values taken as 100%. The concentration of norepinephrine tended to increase in several brain areas examined but, the change was statistically significant only in olfactory tubercles and cerebral cortex. The level of norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol, was lowered to 63% in whole brain of animals given MIF-1 at the dose of 5 mg/kg. These data suggest that MIF-1 enhances the turnover of dopamine and norepinephrine in the brain. However, MIF-1 treatment seemed to produce no consistent change in brain serotonin turnover. In striatum and cortex, this neuropeptide increased serotonin but elevated the level of its metabolite, 5-hydroxyindoleacetic acid indicating that the release of this brain amine was decreased in these two brain regions. The levels of 5-hydroxyindoleacetic acid were enhanced in hypothalamus and pons-medulla regardless of the dose of MIF-1 administered.
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PMID:MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions. 612 14

Behavioural and biochemical studies were carried out in rats given a single daily dose (1 mg/kg, i.p.) of haloperidol for 30 days and subsequently withdrawn for 7 days. Long-term administration of haloperidol resulted in supersensitivity of dopamine receptors. This was manifested by enhanced stereotypic biting, rearing, locomotor and floor activity of haloperidol withdrawn rats when challenged to a low dose of apomorphine (0.5 mg/kg, s.c.) on the 8th day. Chronic haloperidol treatment significantly decreased dopamine synthesis and release as evidenced by low activity of tyrosine hydroxylase and low level of homovanillic acid in striatum. Dopamine levels did not change in the frontal cortex, striatum and midbrain. Haloperidol treatment significantly increased striatal gamma-aminobutyric acid content and glutamic acid decarboxylase activity by 17% and 16% respectively. The decreased tyrosine hydroxylase activity and homovanillic acid level in corpus striatum might, in part, be due to an inhibitory effect of GABAergic neurons on dopaminergic system. Rats withdrawn from chronic haloperidol treatment showed significant increases in GABA level and glutamic acid decarboxylase activity. This probably resulted in further inhibition of dopamine release as evidenced by marked accumulation of dopamine in the corpus striatum and midbrain. No significant alterations in the endogenous levels of norepinephrine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed in haloperidol-treated and subsequently withdrawn rats. These data suggest that chronic haloperidol treatment and subsequent withdrawal results in the development of behavioural dopamine supersensitivity as well as biochemical alterations in dopaminergic and GABAergic system. The changes in these two neuronal systems seem to be interrelated.
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PMID:Behavioural and biochemical alterations following haloperidol treatment and withdrawal: the animal model of tardive dyskinesia reexamined. 613 27

A single dose (17.5 mg/kg i.p.) of methamphetamine was administered to iprindole-treated (10 mg/kg i.p.) rats. Forebrain concentrations of methamphetamine and amphetamine were significantly increased in iprindole-treated rats 1 and 6 hr after injection; in contrast to rats pretreated with saline, both amines were also detected after 18 hr. Three and 7 days after injection, significant decreases were seen in tryptophan hydroxylase (TPH) activity and serotonin concentrations in the cerebral cortex, neostriatum and hypothalamus. Hypothalamic TPH activity had recovered by 14 days. Neostriatal tyrosine hydroxylase activity and dopamine concentrations were significantly depressed at all time points examined. Iprindole alone produced a significant increase in cortical TPH activity after 1 day. After 3 days, TPH activity was significantly decreased when compared with control, whereas serotonin and 5-hydroxyindoleacetic acid concentrations were significantly increased. This study demonstrates that persistence of methamphetamine and/or amphetamine at the site of action is important for neurotoxicity.
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PMID:Effects of a single dose of methamphetamine and iprindole on the serotonergic and dopaminergic system of the rat brain. 618 15


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