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)

Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons.
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PMID:Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems. 1 53

Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses.
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PMID:Molecular mechanisms in the actions of morphine and viminol (R2) on rat striatum. 23 24

The ventral tegmental area (VTA) and its dopaminergic projections appear to mediate some of the rewarding properties of opiates, cocaine, and other drugs of abuse. In a previous study, we demonstrated that chronic morphine and cocaine exert common actions on tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in this dopaminergic brain reward region (Beitner-Johnson and Nestler, 1991). In the present study, we investigated the effects of chronic morphine and cocaine on other phosphoproteins in the VTA by back phosphorylation and two-dimensional electrophoretic analysis. It was found that a number of phosphoproteins, in addition to tyrosine hydroxylase, were regulated similarly by the two drug treatments in this brain region. Several of these morphine- and cocaine-regulated phosphoproteins were identified as neurofilament (NF) proteins. Chronic, but not acute, administration of either morphine or cocaine was found to decrease levels of the three NF proteins, NF-200 (NF-H), NF-160 (NF-M), and NF-68 (NF-L), by between 15% and 50% in the VTA by back phosphorylation, immunolabeling, and Coomassie blue staining. Such regulation of NF proteins was selective, in that no detectable changes were observed in the levels of eight other major cytoskeletal or cytoskeletal-associated proteins analyzed. Furthermore, NF levels were not altered by chronic treatment with either imipramine or haloperidol, two psychotropic drugs without reinforcing properties, or by chronic stress. Morphine and cocaine regulation of NFs showed regional specificity, as NF levels were not altered in the substantia nigra, or other parts of the brain or spinal cord, by these drug treatments. NFs are thought to function as determinants of neuronal morphology and to be associated with axonal transport. Thus, decreased NF levels in the VTA in response to chronic morphine and chronic cocaine could lead to drug-induced alterations in the structural and functional properties of this brain region, which may represent, in turn, part of a common biochemical basis of morphine and cocaine addiction and craving.
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PMID:Neurofilament proteins and the mesolimbic dopamine system: common regulation by chronic morphine and chronic cocaine in the rat ventral tegmental area. 137 74

We studied levels of tyrosine hydroxylase immunoreactivity and phosphorylation state in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in an effort to understand better the mechanisms by which these brain reward regions are influenced by opiates and cocaine. In the VTA, chronic, but not acute, administration of either morphine or cocaine increased levels of tyrosine hydroxylase immunoreactivity by 30-40%, with no change observed in the relative phosphorylation state of the enzyme. In the NAc, chronic, but not acute, morphine and cocaine treatments decreased the phosphorylation state of tyrosine hydroxylase, without a change in its total amount. In contrast, morphine and cocaine did not regulate tyrosine hydroxylase in the substantia nigra or caudate/putamen, brain regions generally not implicated in drug reward. Morphine and cocaine regulation of tyrosine hydroxylase could represent part of a common biochemical basis of morphine and cocaine addiction and craving.
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PMID:Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions. 167 65

The effects of morphine and naloxone on hypothalamo-pituitary-adrenocortical (HPA) activity and blood pressure were studied in rats in which adrenergic transmission had been impaired pharmacologically. The alpha 1-adrenoceptor antagonist, prazosin and the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (alpha-MPT), increased the hypothalamic corticotrophin releasing factor (CRF) content and the plasma corticotrophin (ACTH) concentration and exaggerated the HPA response to stress. In addition, the spontaneous secretion of CRF by hypothalami in vitro was increased by alpha-MPT-treatment. Morphine enhanced the basal and stress-induced activity of the HPA system in vivo. It also stimulated the secretion of CRF by hypothalami in vitro. Naloxone did not affect resting HPA activity but reduced markedly the stress-induced release of corticotrophin. The effects of morphine and naloxone on the HPA axis, in vivo, were reduced by pretreatment with alpha-MPT and prazosin, respectively. The HPA responses could not be correlated with the changes in blood pressure which the drugs caused. The results suggest that opioid substances stimulate HPA activity by depressing the activity of the adrenergic pathways which inhibit the secretion of CRF.
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PMID:Interrelationships of opioidergic and adrenergic mechanisms controlling the secretion of corticotrophin releasing factor in the rat. 282 23

Adrenal catecholamines and their synthesizing enzymes were monitored during morphine treatment and after naloxone-precipitated morphine withdrawal in the rat. At 2 and 6 hr of withdrawal epinephrine content was reduced to approximately 50 and 45% of control. Five days after withdrawal a significant overshoot in adrenal epinephrine concentration was observed. Morphine treatment increased adrenal tyrosine hydroxylase activity to 160% of control. Precipitation of withdrawal with naloxone further increased adrenal tyrosine hydroxylase activity to 240% of control after 1 day; the enzyme activity returned to control values at day 7. Similar effects, but of lesser magnitude, were observed with locus ceruleus tyrosine hydroxylase activity. No increase in adrenal dopamine-beta-hydroxylase activity was seen until day 3 of withdrawal and this activity peaked at 5 days to 160% of control values. Adrenal phenylethanolamine-N-methyltransferase activity was unchanged during the time course studied. Splanchnicotomy caused depletion of adrenal epinephrine to 60% of control. Morphine withdrawal in these animals caused a further (23%) decrease in epinephrine content. These data show that epinephrine is selectively released from the adrenal medulla during naloxone-precipitated morphine withdrawal in the rat and that this release has both a direct and a centrally mediated component. The possible mechanisms underlying these biochemical changes are discussed.
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PMID:Biochemical correlates of morphine withdrawal. 1. Characterization in the adrenal medulla and locus ceruleus. 286 Feb 39

Naloxone-precipitated morphine withdrawal in the rat has been shown to deplete adrenal epinephrine and to increase adrenal and locus ceruleus tyrosine hydroxylase activities. Administration of clonidine (0.1 - 1.0 mg/kg) through the first 6 hr of withdrawal blocked adrenal epinephrine depletion in a dose-dependent fashion. Clonidine also blocked the increases in tyrosine hydroxylase activity seen in the adrenal and locus ceruleus during withdrawal. Clonidine attenuated the weight loss and inhibited the diarrhea during withdrawal. The alpha-2 adrenergic antagonist yohimbine reversed the effects of clonidine in blocking withdrawal. Morphine withdrawal caused only a slight depletion of epinephrine in the denervated adrenal; however, clonidine (0.3 mg/kg) prevented this decrease. These results suggest that clonidine suppresses adrenal and central adrenergic function during morphine withdrawal. This effect occurs through an alpha-2 adrenergic mechanism, possibly at the level of the locus ceruleus although clonidine appears to also have a direct effect on the adrenal medulla. The results are discussed in terms of adrenergic mechanisms of opiate withdrawal and the actions of clonidine on this syndrome.
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PMID:Biochemical correlates of morphine withdrawal. 2. Effects of clonidine. 403 56

Neonatal treatment with the catecholamine neurotoxin 6-hydroxydopamine (6-OH-DA) leads to permanent noradrenaline (NA) denervations of distant projections (e.g. in the neocortex) with a concomitant NA hyperinnervation in regions close to the perikarya (e.g. in the cerebellum) a "pruning effect' mainly affecting the locus coeruleus NA neuron system. Morphine administration after 6-OH-DA produced a significant potentiation of the 6-OH-DA-induced NA depletion in the olfactory bulb, spinal cord, frontal and occipital cortex, with a tendency for NA to increase in the mesencephalon, pons-medulla and cerebellum, when analysed in the adult stage. Morphine treatment alone had no effects on the NA levels in any region studied. Morphine was found to counteract the NA depletion induced by tyrosine hydroxylase inhibition in neonate rats, indicating that morphine reduces NA turnover. The present results are compatible with the view that morphine potentiates the 6-OH-DA-induced degeneration of NA nerve terminals, possibly related to the inhibitory action on NA neurons.
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PMID:Effects of morphine on the 6-hydroxydopamine induced changes of the postnatal development of central noradrenaline neurons. 612 45

Recent studies have shown that biologically active peptides and monoaminergic neurotransmitters coexist in certain neuronal cell populations. Using the immunofluorescence technique, we have examined the localization of enkephalins, vasoactive intestinal peptide (VIP) and tyrosine hydroxylase in the adrenal gland of the frog Rana ridibunda. Most chromaffin cells which stained for tyrosine hydroxylase contained VIP-like immunoreactivity, whereas methionine- (Met-) and leucine- (Leu-) enkephalin-like immunoreactivity was detected in about 40% of the cells revealed by the anti-tyrosine hydroxylase serum. No VIP- or enkephalin-like immunoreactive nerve fibres were observed. Since in the frog, the chromaffin cells are in close contact with the adrenocortical (interrenal) tissue, a possible action of VIP and opiates on corticosteroidogenesis has been investigated. At doses 10(-6) and 10(-5) M, 20-min infusions of synthetic porcine or chicken VIP elicited a significant increase in corticosterone and aldosterone production by perifused frog adrenals, in a dose-dependent manner. As compared to ACTH, VIP was several orders of magnitude less effective in stimulating corticosteroid production. Morphine, Met- and Leu-enkephalins (10(-5) M) had no effect on spontaneous secretion of corticosteroids. In addition, Met- and Leu-enkephalins (10(-5) M) did not alter the production of corticosterone induced by ACTH. THese results suggest that VIP contained in the chromaffin cells of the frog adrenal gland may exert a local action in stimulating corticosteroid production by the interrenal tissue.
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PMID:Co-localization of vasoactive intestinal peptide (VIP) and enkephalins in chromaffin cells of the adrenal gland of amphibia. Stimulation of corticosteroid production by VIP. 613 69

On the basis of biochemical indices of dopamine (DA) nerve activity (decline of DA after inhibition of tyrosine hydroxylase, accumulation of DOPA after inhibition of DOPA decarboxylase) it was revealed that morphine increases the activity of nigrostriatal and mesolimbic DA nerves which terminate in the striatum, nucleus accumbens and olfactory tubercle, but reduce the activity of tuberoinfundibular DA nerves which terminate in the median eminence. Morphine had no effect on tuberohypophyseal DA nerves which project to the posterior pituitary. Naloxone was without effect per se, but blocked the effects of morphine on DOPA accumulation. Thus, morphine differentially alters the diverse DA neuronal systems in the rat brain.
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PMID:Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems. 677 40


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