Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:C-type natriuretic peptide stimulates catecholamine synthesis through the accumulation of cyclic GMP in cultured bovine adrenal medullary cells. 790 32

3-Chloro-L-tyrosine (3CT) is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis. In vivo inhibition of tyrosine hydroxylase results in lower catecholamine levels. 3CT (0.5 mg/kg), administered as a bolus i.v. to anesthetized uninephrectomized rats, elicited increases of 72% and 44% in urinary sodium concentration and volume, respectively, whereas a dose of 1 mg/kg caused increases of 27% and 29%. 3CT, 1 mg/kg, resulted in a 2-fold increase in plasma aldosterone (ALD); 0.5 mg/kg was without significant effect. At a dose of 1 mg/kg 3CT significantly antagonized the renal effects of atrial natriuretic peptide (ANP) (1.5 micrograms kg-1 min-1 by intrarenal infusion), expressed as an enhanced excretion of urine volume (102 +/- 14 vs. 70 +/- 11 microliters/min) and sodium (16.1 +/- 1.8 vs. 11.5 +/- 1.7 microEq/min) and increased osmolar clearance (171 +/- 12 vs. 144 +/- 13 microliters/min). A dose of 0.5 mg/kg of 3CT did not produce these same responses to ANP. The increased urine flow caused by 3CT may reflect reduced norepinephrine synthesis. The inverse dose-effect relationship of 3CT on urine flow rate may result from concomitant depletion of dopamine (DA) and elevated circulating ALD. The antagonism of 3CT on responses to ANP is not at the receptor level, because 3CT did not compete for [125I] ANP binding or inhibit ANP-stimulated guanylate cyclase in kidney cell membranes. It was proposed that the reduced basal sympathetic and renal DA tone, together with the elevated ALD level, account for this antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chlorotyrosine exerts renal effects and antagonizes renal and gastric responses to atrial natriuretic peptide. 791 Feb 11

Assays were developed to investigate the catalytic potential and apparent expression of tyrosinase activities. Tyrosine hydroxylase activity determined with cell lysates (in vitro), entire fixed cells (postfixation), or intact living cells (in situ), and 3,4-dihydroxyphenylalanine oxidase assayed spectrophotometrically or by 3,4-dihydroxyphenylalanine staining on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, demonstrated the following results: 1) The in situ assay displayed reduced tyrosine hydroxylase activity in all three tyrosinase-positive oculocutaneous albino (OCA) lines except for Chediak-Higashi Syndrome melanocytes, which displayed normal activity; 2) The in vitro assay had comparable activity of tyrosinase-positive OCA melanocytes as controls, except for one tyrosinase-positive OCA cell line, which demonstrated increased activity; 3) The postfixation assay, compared with the in situ assay, had elevated activity (ie. normalization) of tyrosinase in OCA cells but reduced activity in controls; 4) The spectrophotometric assay for 3,4-dihydroxyphenylalanine oxidase activity correlated very well with the tyrosine hydroxylase activity determined by the in vitro assay; 5) sodium dodecyl sulfate-polyacrylamide gel electrophoresis of melanocyte lysates either stained with 3,4-dihydroxyphenylalanine or immunoblotted with anti-tyrosinase detected abnormal tyrosinase bands in the Chediak-Higashi Syndrome and one line of tyrosinase positive OCA melanocytes, and both lines had release of tyrosinase into the growth media. In conclusion, the selection and combination of these tyrosinase assays would be informative for differentiation and characterization of human albinism.
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PMID:Distinguishing between the catalytic potential and apparent expression of tyrosinase activities. 798 19

The dopamine transporter (DAT) and norepinephrine transporter (NET) terminate catecholaminergic neurotransmission at synapses by high-affinity sodium-dependent reuptake into presynaptic terminals, and are the initial sites of action for drugs of abuse and antidepressants. In the present study, we used in situ hybridization combined with immunohistochemistry to study the distribution of DAT and NET mRNA in the adult rat brain. Cells were first immunolabeled with antisera directed against one of the catecholamine-synthetic enzymes, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), or phenylethanolamine-N-methyltransferase (PNMT), in order to identify dopaminergic, noradrenergic, or epinephrine-containing cells. The immunolabeled cells were subsequently assayed for their ability to express catecholamine transporter mRNAs by in situ hybridization using either a rat DAT or NET cRNA probe. All dopaminergic cell groups of the mesencephalon contained high levels of DAT mRNA but only the A12 and A13 dopaminergic cell groups of the diencephalon appear to express detectable levels of DAT. All norepinephrine-containing cell bodies in the brainstem (locus coeruleus and lateral tegmentum) appear to express NET mRNA. In contrast, epinephrine-containing cell bodies of the brainstem do not appear to express NET mRNA, which raises the possibility that epinephrine may utilize a transporter that is distinct from the other bioactive amines, or may act as an endocrine regulator that does not require rapid reuptake mechanisms. Moreover, the cell-type-specific expression of catecholamine transporters suggests that DAT and NET gene expression may be closely linked to cellular mechanisms that specify transmitter phenotype. The termination of neurotransmission is a critical component of neural signaling and depends on the rapid removal of neurotransmitters from the synaptic cleft. Pharmacological evidence indicates that the action of monoamines at the synapse is terminated predominantly by rapid reuptake into presynaptic nerve endings via neurotransmitter-specific, high-affinity, Na(+)-dependent membrane transporter proteins. The cDNAs encoding distinct transporter proteins for the monoamines dopamine, norepinephrine, and serotonin have been cloned, expressed, and characterized in a variety of heterologous systems (Blakely et al., 1991; Giros et al., 1991; Hoffman et al., 1991; Kilty et al., 1991; Pacholczyk et al., 1991; Shimada et al., 1991; Usdin et al., 1991). Although the monoamine transporters share a high degree of sequence homology, they are distinguished by their monoamine substrate specificities and by their differential sensitivities to a wide spectrum of transport antagonists. For example, pharmacological agents that potently inhibit norepinephrine and serotonin transport, such as desmethylimipramine and citalopram, have little effect on the activity of the dopamine transporter (Javitch et al., 1983).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cell-type-specific expression of catecholamine transporters in the rat brain. 804 59

Dopamine has been well recognized to be a precursor of norepinephrine, exhibiting cardiovascular effects through alpha-adrenoceptor stimulation by norepinephrine production and release in sympathetic nerve endings. It also has the specific and unique effects of natriuresis and vasodilation. Since dopamine is one of the important endogenous hypotensive and natriuretic substances, it is speculated that impaired dopamine generation and/or the disturbance of the effects of dopamine could cause hypertension with suppression of plasma renin activity and/or salt-sensitivity. A non-specific enzyme of aromatic L-amine acid decarboxylase (AAAD) converting from 3,4-dihydroxyphenylalanine (DOPA) to dopamine is widely distributed in the peripheral tissue, e.g. the sympatho-adrenomedullary system, the small intestine, the lung, the liver, the kidney, etc. Since tyrosine hydroxylase is a rate-limiting enzyme of catecholamine biosynthesis, DOPA generation in the neuronal tissues is accelerated with the sympathetic nerve activation by stress such as emotional and environmental changes, resulting in an increase of DOPA delivery to the non-neuronal tissues containing non-neuronal AAAD. More than five receptors for dopamine are cloned in the brain, and it is suggested that more than three different types of dopamine receptors are in the peripheral tissues. In spontaneously hypertensive rats, the post-receptor defect of renal dopamine D1-receptor has been proposed where peripheral dopamine generation compensatorily increased. In Dahl salt-sensitive rats, another model of genetic hypertension, the blunted response of urinary dopamine to sodium loading has been demonstrated. It is controversial whether abnormalities of the neuronal and/or non-neuronal (particularly renal) dopamine system play a contributory role on the pathogenesis of essential hypertension. However, it is plausible that the impairment of dopamine generation and/or the defective responses of a dopamine receptor might induce sodium retention and hypertension.
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PMID:[Dopamine and hypertension]. 826 73

The effect of supramaximal electric field stimulation on [3H]dopamine (DA) release by rat adrenal capsule-glomerulosa preparations was studied using a micro-volume perfusion system. When the tissues were preloaded with [3H]DA, a considerable amount of [3H]DA and [3H]noradrenaline (NA) were released in response to field stimuli. Reserpinization, calcium removal or tetrodotoxin blocking of Na+ influx all completely inhibited the stimulation-evoked release of DA/NA, indicating that the radioactivity released is of neuronal and vesicular origin. In the adrenal cortex, a substantial proportion of tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactive nerve fibres and varicosities were observed around the zona glomerulosa. DA-containing nerves were not seen in the adrenal cortex; however, the same immunocytochemical procedures clearly demonstrated dopaminergic nerve cells and fibres in the substantia nigra and the striatum respectively, and cells of the adrenal medulla. Like the NA release from noradrenergic varicosities in the zona glomerulosa, the DA release from noradrenergic endings is not subject to negative feedback modulation through DA2 receptors since apomorphine, a DA2-receptor agonist, and sulpiride, a selective DA2-receptor antagonist, failed to affect the release. After in-vivo i.v. administration of [3H]DA, the glomerulosa content of DA and NA and the in-vitro release of [3H]DA and [3H]NA of zona glomerulosa both increased, indicating that the local varicose axon terminals were able to accumulate DA from the circulation, convert it into NA and release it in response to neural activity. This local arrangement of noradrenergic axon terminals, able to take up DA from the circulation and release it or convert it into NA, provides the possibility of a fine tuning of local circulation and aldosterone synthesis in the zona glomerulosa.
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PMID:Dopamine is taken up from the circulation by, and released from, local noradrenergic varicose axon terminals in zona glomerulosa of the rat: a neurochemical and immunocytochemical study. 830 58

Nigrostriatal dopaminergic neurons play an essential role in the central regulation of motor functions. These functions are initiated through the release of dopamine from axon terminals in the striatum or from dendrites in the substantia nigra (SN) and are terminated by the reuptake of dopamine by the sodium- and chloride-dependent dopamine transporter (DAT). DAT also can transport dopamine neurotoxins and has been implicated in the selective vulnerability of nigrostriatal dopaminergic neurons in major models of Parkinson's disease. We have used electron microscopic immunocytochemistry with an N-terminal domain anti-peptide antibody to examine the subcellular distribution of DAT in the rat SN and dorsolateral striatum. In the SN, immunogold labeling for DAT was localized to cytoplasmic surfaces of plasma membranes and smooth endoplasmic reticulum of dendrites and dendritic spines, few of which contained synaptic vesicles. Neuronal perikarya in the SN contained immunogold-labeled pleomorphic electron-lucent tubulovesicles but showed immunolabeling of plasma membranes only rarely. Axon terminals in the striatum contained extensive immunogold labeling of cytoplasmic surfaces of plasma membranes near aggregates of synaptic vesicles and less frequent labeling of intervaricose segments of plasma membrane or small electron-lucent vesicles. In sections dually labeled for DAT and the catecholamine-synthesizing enzyme tyrosine hydroxylase, both markers were colocalized in most profiles in the SN and striatum. These findings support the proposed topological model for DAT and suggest that this transporter is strategically located to facilitate uptake of dopamine and neurotoxins into distal dendritic and axonal processes of nigrostriatal dopaminergic neurons.
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PMID:The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons. 855 28

CATH.a is a central nervous system (CNS) catecholaminergic cell line derived from a transgenic mouse carrying the SV40 T antigen oncogene under the transcriptional control of regulatory elements from the rat tyrosine hydroxylase gene (Suri et al., 1993). CATH.a cells express several differentiated neuronal characteristics including medium and light chain neurofilament proteins, synaptophysin, tyrosine hydroxylase, and dopamine beta-hydroxylase; they synthesize dopamine and norepinephrine. Conversely, they do not express glial-specific fibrillary acidic protein. To establish definitively that CATH.a cells are of neuronal origin, we characterized the repertoire of voltage-gated inward currents expressed by CATH.a cells. Such inward currents are necessary for neuronal excitability. We report that all CATH.a cells possess a tetrodotoxin-sensitive sodium current (peak amplitude = 590 +/- 319 pA) and 68% possess a high voltage-activated calcium current (peak amplitude = 175 +/- 67 pA). Pharmacological analyses suggest that individual cells express varying levels of L- and N-type calcium current, but no P-type current. In addition, in 55% of the cells with a calcium current, about a half of this current is resistant to selective antagonists for L- and N-type currents, suggesting that another calcium current exists in these CATH.a cells which is not L-, N-, or P-type. The heterogeneous pattern of current detected persisted in several CATH. a subclones, suggesting that factors other than genetic variability influence current expression. The demonstration that CATH.a cells express these currents indicates that they have excitable membrane properties characteristic of neurons. Although many peripheral nervous system (PNS) cell lines exist, very few CNS cell lines with differentiated neuronal properties exist. Since the CATH.a cells can be grown continuously in large amounts, they may be useful for purifying, characterizing, and/or cloning various neuronal-specific molecules and thereby may add to our understanding of CNS catecholaminergic neurons.
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PMID:A CNS catecholaminergic cell line expresses voltage-gated currents. 866 8

Neurons immunoreactive for Fos, the protein product of the immediate early gene c-fos, have been compared in the rostral ventral medulla and spinal cord of conscious normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) after baroreceptor unloading. Hypotension induced by a 60-minute intravenous infusion of sodium nitroprusside reduced baroreceptor activity; controls received intravenous saline. In WKY, 474 +/- 56 (n=6) Fos-positive neurons were identified in the rostral ventral medulla after nitroprusside infusion, a fivefold increase from controls; 50% of the tyrosine hydroxylase-containing neurons in the rostral ventral medulla were activated by this hypotension. Sympathetic preganglionic neurons, mainly sympathoadrenal neurons, were Fos positive after nitroprusside, but Fos-positive sympathetic preganglionic neurons were not observed in control WKY. In SHR, Fos immunoreactivity in the rostral ventral medulla was elevated in the control group compared with the WKY controls (236 +/- 31 and 93 +/- 15, respectively, n=6 for both). Nitroprusside hypotension did not further increase Fos immunoreactivity in the rostral ventral medulla, although the number of Fos-positive spinal sympathetic neurons increased. Our results have identified different neuronal activities between WKY and SHR in sites that are critical to sympathetic outflow. In WKY, nitroprusside effects are consistent with an activation of rostral ventral medulla neurons, including bulbospinal neurons, that are normally inhibited by baroreceptor activity. In SHR, basal nerve activity is increased, so even at rest, rostral ventral medulla neurons and sympathetic preganglionic neurons, mainly sympathoadrenal neurons, are Fos immunoreactive. These activated neurons are likely to contribute to the elevated blood pressure in this rat strain.
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PMID:Altered c-fos in rostral medulla and spinal cord of spontaneously hypertensive rats. 869 50

Neural networks that mediate the reflex response to baroreceptor withdrawal were explored in Sus scrofa. Induction of c-fos was used as a monitor of synaptic activity in response to hypotension sustained by systemic administration of a peripheral vasodilator, sodium nitroprusside. Patterns of c-fos gene expression were compared between Saffan-anesthetized experimental animals and age-matched normotensive controls administered vehicle. Effects of other variables were controlled including 1 h preoperative accommodation to the novel environment, anesthesia, blood gases and pH. Identical post-stimulus survival periods were allowed for accumulation of transcript. The c-fos protein, Fos, was identified immunocytochemically with two rabbit antisera raised against amino acids 1-131 of Fos or residues 4-17 of synthetic human transcript. Fos was identified in catecholaminergic neurons labeled with an antiserum to tyrosine hydroxylase (TH). Fos was induced in the nucleus tractus solitarii (NTS) of hypotensive piglets. Neurons encoding Fos matched projection patterns of first order visceral afferents. Induction was prominent in the dorsolateral nucleus coinciding with the baroreceptor field. Indices of increased neuronal activity were evident in other baroreceptor terminal sites, e.g., medial subnucleus, the medial commissural field, the intermediate subnucleus and a ventral A2 noradrenergic area. In reticular formation c-fos protein was induced in circumscribed columns in the lateral tegmental field (LTF) extending from facial nucleus to calamus scriptorius. Catecholaminergic (TH-positive) neurons expressed Fos in the porcine C1 and A1 areas of ventrolateral medulla. Fos was also induced in a dorsal intermediate reticular zone of LTF. Minor or inconsistent differences between experimental and control were observed in nucleus raphe pallidus, rostral paramedian reticular formation, upper thoracic intermediolateral cell column, and stellate ganglia. In conclusion, baroreceptor withdrawal in young animals induced patterns of neuronal response along established cardiovascular reflex pathways.
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PMID:Hypotension-induced expression of the c-fos gene in the medulla oblongata of piglets. 882 57


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