Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we reported that a single injection of nicotine decreased AP-1 DNA binding activity in adrenal medullae, although chronic bidaily nicotine (and saline) injections increased this binding activity [15]. Repeated acute nicotine injections (3 mg/kg i.p., 7 injections equi-spaced over a 3 h period) effectively increased adrenal tyrosine hydroxylase [3] and [Met5]enkephalin levels and also profoundly decreased adrenal medulla AP-1 DNA binding activity for over 8 h.
Brain Res Mol Brain Res 1995 Jul
PMID:Acute repeated nicotine injections increase enkephalin and decrease AP-1 DNA binding activity in rat adrenal medulla. 747 31

Nicotine, a major pharmacologically active component of tobacco smoke, is generally believed to be one of the factors responsible for the deleterious consequences of cigarette smoking. Nicotine activates the sympathoadrenal system and increases the synthesis and release of catecholamines into circulation. In this study we show that single and repeated injections of nicotine increase the expression of tyrosine hydroxylase (TH), a rate limiting enzyme in the catecholamine biosynthetic pathway. These treatments also regulated the expression of dopamine beta-hydroxylase (DBH) and neuropeptide Y (NPY) in rat adrenals. The effect of nicotine on several transcription factors in the adrenal medulla was examined. Nicotine administration by injection increased the phosphorylation of CREB and induced c-Fos protein without affecting members of the jun family. In contrast to the results with injections, continuous infusion via osmotic pumps did not affect any of these parameters. These data indicate that activation of several transcription factors and increased expression of TH, DBH, and NPY is dependent on the mode of nicotine administration.
Brain Res Mol Brain Res 1995 Aug
PMID:Nicotine elicits changes in expression of adrenal catecholamine biosynthetic enzymes, neuropeptide Y and immediate early genes by injection but not continuous administration. 749 48

Males housed in mixed sex groups quickly form dominance hierarchies; subordinates can be further subdivided into stress responsive subordinates (SRS) and non-responsive subordinates (NRS) based on corticosterone responses to a novel stressor. Tyrosine hydroxylase (TH) mRNA levels measured with in situ hybridization were elevated in locus coeruleus (LC) of NRS compared to singly or pair-housed controls; NRS also had higher TH levels than dominants. TH protein levels determined by immunoautoradiography were also higher in LC of NRS and SRS versus pair-housed controls.
Brain Res Mol Brain Res 1995 Aug
PMID:Effects of chronic social stress on tyrosine hydroxylase mRNA and protein levels. 749 59

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)
Brain Res Mol Brain Res 1994 Mar
PMID:Effect of morphine on hypothalamic tyrosine hydroxylase mRNA levels in dopaminergic neurons and on preoptic DOPAC levels measured by microdialysis. 751 96

With in situ hybridization we examined the localization of mRNA coding for tyrosine hydroxylase (TH) in the rat hypothalamo-neurohypophysial system (HNS) under conditions of acute osmotic stress. Fifteen min after salt loading, hybridization signal of TH mRNA could be located in the magnocellular hypothalamic nuclei and in the median eminence (ME). In untreated animals, TH mRNA was detected only in the ME. In osmotically challenged animals that had been pretreated with colchicine, signals for TH mRNA remained confined to the ME, while pretreatment of salt loaded rats with a polymerase II transcription inhibitor resulted in labelling of the magnocellular perikarya but a decrease of the hybridization signal in the ME. Our results suggest that also TH mRNA is among the RNAs which are axonally transported in the HNS. TH mRNA can probably be stored in axons of the hypothalamo-neurohypophysial tract, to be transported retrogradely and translated upon certain stimuli.
Brain Res Mol Brain Res 1994 Apr
PMID:Localization of tyrosine hydroxylase mRNA in the axons of the hypothalamo-neurohypophysial system. 751 30

Several lines of anatomical, neurochemical, electrophysiological, and behavioral evidence suggest the existence of physiological interactions between neurotensin (NT) and the brain dopaminergic systems. Thus, NT has been shown to exert a neuroleptic-like action and could be implicated in the pathogenesis and treatment of schizophrenia. It is thus of particular importance to develop in vitro cell culture systems as models to study such interactions. Rat adrenal pheochromocytoma PC12 cells, which expressed high levels of tyrosine hydroxylase, were used in the present study. In contrast to rat brain cells in primary cultures, PC12 cells did not express functional NT receptors. However, they were able to express both NTmRNA and NT in response to NGF, forskolin, and dexamethasone. Those neurochemical modifications furthermore may be related to changes in the morphology of the PC12 cells in response to NGF, forskolin, and dexamethasone alone or in combination. These data suggest that PC12 cells may provide a useful model to study in vitro the regulation of both catecholamine and neurotensin phenotypes.
Mol Neurobiol
PMID:Treatment of PC12 cells by nerve growth factor, dexamethasone, and forskolin. Effects on cell morphology and expression of neurotensin and tyrosine hydroxylase. 757 2

We amplified, via PCR, DNA segments from intron 1 of the tyrosine hydroxylase gene (TH01) and intron 40 of the von Willebrand factor gene (VWA) in ten nonhuman primate genera. In humans both introns contain polymorphic microsatellites with tetrameric repeats. Compared to the allelic ranges in human populations relatively short repeat arrays could be detected for the nonhuman primates typed, presumably reflecting an ancient precursor state at both microsatellite loci. Furthermore, our results provide evidence for an association of the average number of repeats present in different primate genera and their divergence time from man. DNA sequencing of VWA orthologues revealed a relatively high variability in the arrangement of repeats in the 5'-repeat arrays, the generation of which could probably be explained by polar mutational events.
J Mol Evol 1995 Jul
PMID:Microsatellite polymorphisms reveal phylogenetic relationships in primates. 760 83

The nicotinic agonist dimethylphenylpiperazinium (DMPP) transiently stimulates tyrosine hydroxylase (TH) gene transcription in cultured bovine adrenal chromaffin cells (Craviso et al., J. Neurochem., 59 (1992) 2285-2296). The present studies examined the mechanism of this stimulation, exploring the hypothesis that c-fos- and/or cyclic AMP-related mechanisms are involved. As determined by nuclear run-on assay, exposure of chromaffin cells to DMPP (1 microM) induced c-fos and TH gene transcription fivefold and twofold, respectively. Nitrendipine (20 microM) blocked both responses, indicating a similar dependency of each on extracellular calcium. Both c-fos and TH gene transcription rates were also elevated by entry of calcium due to the presence of the calcium ionophore A23187 (5 microM). Comparison of the time dependence of the DMPP stimulation of c-fos and TH gene transcription revealed similar time courses. Both were rapid and transient, peaking within 10-30 min of nicotinic receptor occupancy and returning to control values by 1 h. This simultaneous activation of the TH and c-fos genes indicates that Fos induction cannot be responsible for the stimulation of TH gene transcription. This conclusion was further supported by a failure of anisomycin (100 microM) pretreatment of chromaffin cells, which blocked protein synthesis 99%, to have any effect on either the rapid stimulation of TH gene transcription or the length of time that the TH gene was activated by DMPP. Thus, neither Fos nor other high turnover-rate transcription factors appear to be responsible for the stimulation, or return to control level, of TH gene activity following nicotinic stimulation of chromaffin cells. In other experiments, treating chromaffin cells with a combination of maximally effective concentrations of DMPP and forskolin was found to produce no greater stimulation of TH gene transcription than either agent alone, suggesting that DMPP acts through the same mechanism as forskolin. Taken together, these results support the conclusion that the mechanism of TH gene activation in chromaffin cells by DMPP involves a cyclic AMP-dependent process and not the induction of transcription factors such as Fos.
Brain Res Mol Brain Res 1995 Apr
PMID:The transient nicotinic stimulation of tyrosine hydroxylase gene transcription in bovine adrenal chromaffin cells is independent of c-fos gene activation. 760 11

Effects of destruction of central dopaminergic neurons on tyrosine hydroxylase gene expression were investigated. Two weeks after the unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, a 67% to 99% loss of striatal dopamine (DA) content was observed ipsilateral to the injection site. Measures of tyrosine hydroxylase (TH) protein levels revealed losses in striatal content proportional to DA content. Striatal dihydroxylphenylacetic acid (DOPAC) was somewhat less affected, resulting in 2- to 4-fold increases in the striatal DOPAC/DA ratio, depending on the severity of the lesion. Morphologically, surviving TH-positive substantia nigra pars compacta (SNc) neurons were more rounded than contralateral control cells, and exhibited decreases in cross-sectional area that were proportional to the loss of striatal DA. Measures of cytoplasmic TH mRNA levels in surviving neurons by in situ hybridization autoradiography revealed a significant 23% decrease in TH content per cell that could be correlated to lesion size. The decreases in cross-sectional area and TH mRNA content resulted in a small decrease in TH mRNA density of 6%. The determination of TH transcription rate by an intron-directed in situ hybridization assay found no significant change in TH transcriptional activity as a function of lesion. We conclude that the short-term effect of partial 6-OHDA-induced lesions of the nigrostriatal dopaminergic pathway is the selective loss or shrinkage of large DA neurons of the SNc, and that the associated down-regulation of TH mRNA expression in surviving neurons is due to a post-transcriptional mechanism related either to concomitant cellular hyperactivity or is secondary to the morphological alterations.
Brain Res Mol Brain Res 1995 Apr
PMID:Alterations in tyrosine hydroxylase expression following partial lesions of the nigrostriatal bundle. 760 16

1. The aim of this study was to investigate the neurochemical effects and measure the anatomical spread of infusion of c-fos antisense (AS) DNA into the striatum. 2. Rats were anesthetized and infused in opposing striata with c-fos AS and c-fos sense (S) DNA. Ten hours later they were injected with apomorphine (2 mg/kg, i.p.) and 20 min later they were overdosed with sodium pentobarbital and their brains either perfused or frozen. Vibratome-cut sections were immunostained for the detection of c-fos, JunB, Krox 24, somatostatin, substance P, dynorphin, tyrosine hydroxylase, and enkephalin. Cryostat-cut sections from the caudate were immunostained for the detection of c-fos, JunB, and Krox 24, as well as in situ hybridization for proenkephalin mRNA. Sections from the globus pallidus were used for the autoradiographic localization of D2 dopamine and A2a adenosine receptors. Sections from the substantia nigra were used for the autoradiographic localization of D1 dopamine and cannabinoid receptors. A second group of rats were injected in opposing striata with biotin-labeled c-fos AS DNA and c-fos S DNA. Ten hours later they were challenged with apomorphine (2 mg/kg, i.p.) and 20 min later brains were either perfused or frozen. Sections from these brains were cut throughout the rostral-caudal extent of the forebrain and the biotin labeled AS DNA was localized. 3. Krox 24 was expressed at high levels on the sense side of the brain in the striatum and overlying neocortex. However, on the AS-injected side there was a reduction in Krox 24 expression in striatum and overlying cortex. The biotin-labeled AS studies confirmed that the striatal infusion spread throughout the dorsal striatum as well as the overlying neocortex. We did not detect any changes in neurotransmitter receptors, neuropeptides, or tyrosine hydroxylase in AS/S-injected rat brains. 4. These results demonstrate that c-fos AS reduces Krox 24 expression in striatal and neocortical neurons but does not change the expression of a number of other proteins involved in basal ganglia function. Whether this effect is due to nonspecific actions of c-fos AS or to its effects on a component of the transduction pathway responsible for basal Krox 24 expression (NMDA receptors?) is unknown.
Cell Mol Neurobiol 1994 Oct
PMID:c-fos antisense reduces expression of Krox 24 in rat caudate and neocortex. 762 2


<< Previous 1 2 3 4 5 6 7 8 9 10