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)

A chemical assay of tyrosine (Tyr) in nervous tissue is described. The method is based on a rapidly performed isolation of Tyr on small Sephadex G 10 columns, followed by reverse-phase HPLC in conjunction with amperometric detection. The method permitted the additional quantification of 3,4-dihydroxyphenylalanine, dopamine (DA), and its acidic metabolites. The method was applied to a study of the effects of gamma-butyrolactone, haloperidol, haloperidol in combination with amfonelic acid, morphine, NSD 1015, and tyrosine methylester on the concentration of Tyr in the striatum, frontal cortex, hypothalamus, and cerebellum of rat brain. The effect of tyrosine methylester on DA and its acidic metabolites was investigated in the striatum and frontal cortex. Morphine and NSD 1015 were found to increase Tyr levels. gamma-Butyrolactone, haloperidol, and haloperidol combined with amfonelic acid decreased the Tyr content in a manner related to their stimulatory effect on DA biosynthesis. These effects were restricted to DA-rich brain areas. It was concluded that during conditions of increased DA biosynthesis, the Tyr pool still possesses a considerable reserve capacity. The results bring into question the concept that brain Tyr is an important additional factor controlling catechol synthesis during increased tyrosine hydroxylase activity.
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PMID:On the significance of tyrosine for the synthesis and catabolism of dopamine in rat brain: evaluation by HPLC with electrochemical detection. 682 72

Morphine not only suppresses norepinephrine-induced increases in LHRH mRNA levels but, in these same animals, it simultaneously amplifies norepinephrine (NE)-induced LH release. These observations suggest that NE may activate parallel mechanisms which independently increase LHRH mRNA levels and LHRH release and suggest that some of these effects could be mediated indirectly via morphine's action on different components of the hypothalamic dopamine (DA) system. Accordingly, in the present studies we examined the effects of morphine on various components of this dopamine system using as our index of altered DA neuronal activity, the changes which occur in tyrosine hydroxylase (TH) mRNA levels following morphine. As an ancillary index of changes which occur in dopamine neuronal activity, we measured, by microdialysis, the changes which occur in preoptic dihydroxyphenylacetic acid (DOPAC) levels after either subcutaneous injections or following microinfusions of morphine into the zona incerta (ZI). In a final study, we evaluated whether DA when given alone (icv infusion) or prior to icv NE would altered LH release. Single cell levels of TH mRNA in preoptic A15 and periventricular anterior hypothalamic A14 DA neurons were not affected by morphine 1, 5 and 24 h later. In contrast, within 1 h after morphine, TH mRNA levels in ZI A13 neurons were significantly elevated and they remained high at 5 nd 24 h compared to controls. Morphine also resulted in a significant rise in TH mRNA levels in tuberoinfundibular DA neurons (TIDA) (A12) within 1 h and these levels remained high to 5 h. Thereafter, by 24 h, message levels had returned to control values. Morphine also resulted in a rapid rise in plasma prolactin (Prl) with peak values occurring at 20 min and then returning to baseline by 90 min. When morphine was given sc it resulted, within 15 min, in a rapid rise in preoptic DOPAC levels and these levels continued to rise such that they were 217% higher than pretreatment values by 105 min. Preoptic 5-hydroxyindoleacetic acid (5-HIAA) levels also increased by 25-75% after sc morphine. The microinfusion of morphine into ZI also resulted in elevated preoptic DOPAC but not 5-HIAA levels within 15 min. The icv infusion of DA alone had no effect on plasma LH whereas, NE (icv) produced a modest but significant increase in plasma LH. When DA was given 15 min prior to the infusion of NE, neither amplification nor inhibition of NE-induced LH release occurred. From these and other studies we conclude that the morphine-induced suppression of TIDA neuronal activity may allow NE to release greater amounts of LHRH from axon terminals in the median eminence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of morphine on hypothalamic tyrosine hydroxylase mRNA levels in dopaminergic neurons and on preoptic DOPAC levels measured by microdialysis. 751 96

1. This study aimed to establish the site at which morphine acts to inhibit oxytocin release in response to peripheral administration of cholecystokinin (CCK). 2. Conscious rats were given morphine or vehicle followed by CCK or vehicle (I.V.). Fos immunoreactivity was apparent 90 min after CCK injection in the supraoptic nucleus of vehicle- but not morphine-pretreated animals. 3. In the dorsomedial (C2/A2) and the ventrolateral (C1/A1) regions of the brainstem, about half of the cells immunoreactive for tyrosine hydroxylase (TH) expressed Fos-like protein after CCK injection. In the C2/A2 region, 20% of the Fos-positive cells also showed TH immunoreactivity, whereas in the C1/A1 region 68% did so. Morphine treatment did not significantly change the number of cells expressing Fos immunoreactivity, or the percentage of TH-positive cells expressing Fos-like protein. 4. Amine release was measured in the supraoptic nucleus of urethane-anaesthetized rats using a microdialysis probe. An I.V. injection of CCK increased the concentrations in the dialysate of noradrenaline and serotonin, but not of either adrenaline or dopamine. Pretreatment with morphine (I.V.) blocked the effects of CCK in a naloxone-reversible manner. 5. Inclusion of morphine in the dialysate also blocked the increase in noradrenaline and serotonin in response to CCK in a naloxone-reversible manner. 6. These observations indicate that morphine acts near or within the supraoptic nucleus to block CCK-evoked noradrenaline release presynaptically. This presynaptic action of morphine may be a cause of the blockade of oxytocin release after CCK.
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PMID:Presynaptic actions of morphine: blockade of cholecystokinin-induced noradrenaline release in the rat supraoptic nucleus. 773 Sep 90

The epigenetic stimuli that regulate the development of noradrenergic LC neurons were studied in an vitro system of LC primary cultures. Noradrenergic cells were identified using immunocytochemical staining for tyrosine hydroxylase (TH). Maturation of noradrenergic neurons was assessed by measuring the high affinity uptake of norepinephrine (NE). Coculturing target cells with LC neurons exerts both stimulatory and inhibitory effects on NE uptake, depending on the density of plated cells. The target stimulatory effect may be mediated by glial soluble factors, whereas the inhibitory effect may be mediated by glial membranal molecules. In addition to target derived trophic factors, the effect of elevated cAMP levels was examined. cAMP analogs and forskolin dramatically increase the number of TH+ cells, possibly by supporting their survival. This phenomenon is not dependent on calcium or calcium requiring processes and is not mediated by glial cells. The trophic activity of cAMP appears to be exerted by protein phosphorylation via cAMP dependent protein kinase. Norepinephrine is suggested to be one signal that triggers cAMP elevation through the beta-adrenergic receptor and thereby affects LC development. Morphine, which is known to inhibit adenylate cyclase, reduces NE uptake and number of TH+ neurons. Morphine also inhibits the NT-3 induced increase in noradrenergic survival. We hypothesize that morphine exerts these effects by modulating the cAMP cascade.
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PMID:Locus coeruleus (LC)--target interaction and cAMP in control of LC development. 785 95

We examined the mechanism of the inhibitory effect of prostanoid EP(3) receptor agonists on naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Rats were rendered morphine dependent by subcutaneous (s.c.) implantation of two pellets containing 75 mg morphine for 5 days. Morphine withdrawal syndrome was precipitated by i.p. injection of naloxone (3 mg/kg). Intracerebroventricular (i.c.v.) administration of (+/-)-15alpha-hydroxy-9-oxo-16-phenoxy-17,18, 19,20-tetranorprost-13-trans-enoic acid (M&B28,767: prostanoid EP(3) receptor agonist) or sulprostone (prostanoid EP(1)/EP(3) receptor agonist) significantly suppressed many withdrawal signs. Northern blotting and in situ hybridization studies revealed that i.c.v. administration of M&B28,767 (1 pg/rat) attenuated the elevation of c-fos mRNA during naloxone-precipitated withdrawal in many brain regions, including the cerebral cortex, thalamus, hypothalamus and locus coeruleus. Double in situ hybridization analysis revealed that in the locus coeruleus most of the tyrosine hydroxylase mRNA-positive neurons expressed mu-opioid receptor mRNA and more than half of these neurons were positive for prostanoid EP(3) receptor mRNA. These results indicate that the suppression by prostanoid EP(3) receptor agonists of naloxone-precipitated morphine withdrawal syndrome can be attributed to the inhibition of neuronal activity in several brain regions, including the locus coeruleus, the largest source of central noradrenergic neurons.
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PMID:Possible involvement of the locus coeruleus in inhibition by prostanoid EP(3) receptor-selective agonists of morphine withdrawal syndrome in rats. 1070 32

To investigate the involvement of catecholamines and/or the cyclic AMP (cAMP) systems in the development of drug dependence, we examined whether morphine dependence was developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. Morphine (10 mg/kg) induced place preference in the wild-type mice. In the TH+/- and CBP+/- mice, however, we could not find any morphine-induced place preference. When the wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased numbers of jumping, rearing and forepaw tremor as a sign of withdrawal symptom and increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. However, increased numbers of jumping and forepaw tremor in the TH+/- and CBP+/- mice and increased level of cAMP in the thalamus/hypothalamus of TH+/- mice were not observed. These results suggest that catecholamines and CBP are involved in the development of morphine dependence, and that some changes in the catecholaminergic and/or cAMP system induced by repeated morphine treatment play an important role in the addiction of morphine.
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PMID:[The mechanisms of morphine dependence and it's withdrawal syndrome: study in mutant mice]. 1123 92

We previously demonstrated that morphine withdrawal induced hyperactivity of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN) in rats, in parallel with an increase in the neurosecretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, as evaluated by corticosterone release. These neuroendocrine effects were dependent on stimulation of alpha-adrenoceptors. In the present study, Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurones during morphine withdrawal. Dependence on morphine was induced by 7-day chronic subcutaneous implantation of six morphine pellets (75 mg). Morphine withdrawal was precipitated by administration of naloxone (5 mg/kg subcutaneously) on day 8. Fos immunoreactivity in the PVN and also in the nucleus tractus solitarius (NTS)-A2 and ventrolateral medulla (VLM)-A1 cell groups, which project to the PVN, increased during morphine withdrawal. Following withdrawal, Fos immunoreactivity was present in most of the TH-positive neurones of the A2 and A1 neurones. In a second study, the effects of administration of adrenoceptor antagonists on withdrawal-induced Fos expression in the PVN were studied. Pre-treatment with alpha1- or alpha2-adrenoceptor antagonists, prazosin (1 mg/kg intraperitoneally) and yohimbine (1 mg/kg intraperitoneally), respectively, 20 min before naloxone administration to morphine-dependent rats markedly reduced Fos expression in the PVN. Similarly, pre-treatment with the beta antagonist, propranolol (3 mg/kg intraperitoneally), significantly prevented withdrawal-induced Fos expression. Collectively, these results suggest the hypothesis that noradrenergic neurones in the brainstem innervating the PVN are active during morphine withdrawal, and that activation of transcriptional responses mediated by Fos in the HPA axis following withdrawal are dependent upon hypothalamic alpha- and beta-adrenoceptors.
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PMID:Morphine withdrawal-induced c-fos expression in the hypothalamic paraventricular nucleus is dependent on the activation of catecholaminergic neurones. 1235 36

The recently discovered endogenous peptide orphanin FQ/nociceptin (OFQ/N) activates the opioid receptor-like 1 (ORL1) receptor and produces diverse effects on pain perception. In addition to producing spinal analgesia, OFQ/N also exhibits an 'anti-opioid activity' against functional (supraspinal analgesia) and behavioral (conditioned place preference and withdrawal) properties of morphine. One manifestation of the behavioral changes resulting from chronic use of morphine is the upregulation of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis), which contributes to the dramatic increases in catecholamine release in the target regions of the locus coeruleus (LC) and the ventral tegmental area (VTA). The present study sought to determine the molecular mechanism(s) by which OFQ/N modulates the chronic actions of morphine by utilizing human neuroblastoma cell lines [BE(2)-C and SH-SY5Y] that endogenously express TH, and mu and ORL1 receptors. Activation of mu or ORL1 receptors in these cells in turn activates extracellular signal-regulated protein kinases (ERKs), ERK1 and ERK2. Chronic activation of mu, but not ORL1, receptors upregulated TH levels in these cells as previously reported in rat brain. Morphine-induced TH upregulation was blocked upon inclusion of a MEK-1 (mitogen-activated protein kinase kinase-1) inhibitor (PD98059), confirming the role for ERKs in this adaptive response to morphine. Inclusion of OFQ/N during chronic morphine exposure also blocked morphine-induced TH upregulation. Furthermore, chronic OFQ/N exposure increased levels of the TH gene repressor, Oct-2, irrespective of the presence or absence of morphine. This report suggests a potential role for Oct-2 in mediating the anti-opioid actions of OFQ/N against the behavioral manifestations resulting from chronic use of morphine.
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PMID:Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation. 1239 6

Morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on an hyperactivity of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN). However, the possible adaptive changes that can occur in these pathways during morphine dependence are not known. We studied the alterations in tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamines biosynthesis) immunoreactivity levels and TH enzyme activity in the rat NTS-A2/VLM-A1 noradrenergic cell groups and in the PVN during morphine withdrawal. In the same paradigm, we measured Fos expression as a marker of neuronal activation. TH and Fos immunoreactivity was determined by quantitative Western blot analysis, combined with immunostaining for TH and Fos for immunohistochemical identification of active neurons during morphine withdrawal. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg s.c.). Morphine withdrawal induced the expression of Fos in the PVN and NTS/VLM, which indicates an activation of neurons in these nuclei. TH immunoreactivity in the NTS/VLM was increased 90 min after morphine withdrawal, whereas there was a decrease in TH levels in the PVN at the same time point. Following withdrawal, Fos immunoreactivity was present in most of the TH-positive neurons of the A2 and A1 neurons. TH activity was measured in the PVN, a projection area of noradrenergic neurons arising from NTS-A2/VLM-A1. Morphine withdrawal was associated with an increase in the enzyme activity at different time points after naloxone-precipitated morphine withdrawal. The present results suggest that an increase in TH protein levels and TH enzyme activity might contribute to the enhanced noradrenergic activity in the PVN in response to morphine withdrawal.
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PMID:Regulation of tyrosine hydroxylase levels and activity and Fos expression during opioid withdrawal in the hypothalamic PVN and medulla oblongata catecholaminergic cell groups innervating the PVN. 1253 73

Morphine withdrawal is characterized by functional alterations at the level of the ventrotegmental area. We investigated the effects of chronic morphine administration and withdrawal on the morphological properties of immuno-labelled tyrosine hydroxylase-positive neurons of the rat ventrotegmental area with a confocal laser scanning microscope. Morphological evaluation revealed a reduction in the area and perimeter of tyrosine hydroxylase-positive somata in morphine-withdrawn rats. Conversely, the number of cells per field was found to have increased in the naloxone group. Collectively, the present results indicate that withdrawal from a chronic morphine treatment, and not chronic morphine per se, modifies cellular morphology of tyrosine hydroxylase-positive, presumably dopamine-containing, neurons of the rat VTA. This is consistent with the idea that withdrawal from morphine alters functioning of the mesolimbic dopamine system and provides a direct morphological correlate for the functional abnormalities typical of morphine withdrawal.
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PMID:Morphine withdrawal-induced abnormalities in the VTA: confocal laser scanning microscopy. 1258 Nov 78


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