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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PC12 cells are spherical when cultured on plastic, but flatten and spread extensively when cultured on extracellular matrix (ECM) produced by bovine corneal endothelial cells. We previously demonstrated that cells which have spread on ECM release more dopamine and contain less intracellular dopamine than cells which are rounded on plastic cultureware. Glucocorticoids increase dopamine production in PC12 cells presumably via an increase in tyrosine hydroxylase gene transcription. We questioned whether cell shape as determined by ECM would change the response of PC12 cells to glucocorticoids. Dopamine release and cell content were measured by a radioenzymatic assay in serum-free cultures of PC12 cells on ECM and plastic treated with various glucocorticoids in a dose-response fashion for 24 or 48 h. In addition, the response of cells on both substrata to one dose of dexamethasone was examined from 3-48 h. PC12 cells on ECM and plastic exhibited a dose-related increase in dopamine release and content when treated for 24 h with corticosterone or for 48 h with dexamethasone, corticosterone or cortisol. The ED50s for dexamethasone- and corticosterone-stimulated release and content were similar for cells on ECM and plastic as were the doses at which the first significant increases were detected. The average times at which the first significant increase in release and content occurred were also similar for cells on ECM and plastic. PC12 cells on ECM continue to release more dopamine and store less dopamine than cells on plastic with glucocorticoid treatment. However, glucocorticoid-treated cells on ECM showed a greater percent increase over ECM controls in the cell content of dopamine, whereas glucocorticoid-treated cells on plastic showed a greater percent increase over controls in the release of dopamine. It is hypothesized that glucocorticoids increase dopamine production to a similar extent in cells on ECM and plastic, but that storage is facilitated in cells on ECM.
Mol Cell Endocrinol 1987 Apr
PMID:Glucocorticoid stimulation of dopamine production in PC12 cells on extracellular matrix and plastic. 356 53

Differential screening of cDNA libraries was used to detect and prepare probes for mRNAs that are regulated in PC12 rat pheochromocytoma cells by long-term (2-week) treatment with nerve growth factor (NGF). In response to NGF, PC12 cells change from a chromaffin cell-like to a sympathetic-neuron-like phenotype. Thus, one aim of this study was to identify NGF-regulated mRNAs that may be associated with the attainment of neuronal properties. Eight NGF-regulated mRNAs are described. Five of these increase 3- to 10-fold and three decrease 2- to 10-fold after long-term NGF exposure. Each mRNA was characterized with respect to the time course of the NGF response, regulation by agents other than NGF, and rat tissue distribution. Partial sequences of the cDNAs were used to search for homologies to known sequences. Homology analysis revealed that one mRNA (increased 10-fold) encodes the peptide thymosin beta 4 and a second mRNA (decreased 2-fold) encodes tyrosine hydroxylase. Another of the increased mRNAs was very abundant in sympathetic ganglia, barely detectable in brain and adrenals, and undetectable in all other tissues surveyed. One of the decreased mRNAs, by contrast, was very abundant in the adrenals and nearly absent in the sympathetic ganglia. With the exception of fibroblast growth factor, which is the only other agent known to mimic the differentiating effects of NGF on PC12 cells, none of the treatments tested (epidermal growth factor, insulin, dibutyryl cyclic AMP, dexamethasone, phorbol ester, and depolarization) reproduced the regulation observed with NGF. These and additional findings suggest that the NGF-regulated mRNAs may play roles in the establishment of the neuronal phenotype and that the probes described here will be useful to study the mechanism of action of NGF and the development and differentiation of neurons.
Mol Cell Biol 1987 Sep
PMID:Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells. 367 Mar 9

The effects of lisuride and of the R(-)- and S(+)-enantiomers of apomorphine were examined on 3,4-dihydroxyphenylalanine (DOPA) production by striatal synaptosomes and by crude, soluble striatal tyrosine hydroxylase. Due to their catechol structure, the enantiomers were almost equally effective in blocking soluble tyrosine hydroxylase (EC 1.14.16.2) (IC50 = 470 and 890 nM for R(-)- and S(+)-apomorphine, respectively), provided incubations were performed at pH 7.2 with 1 mM tetrahydrobiopterin as cofactor. The enantiomers were similarly effective in blocking synaptosomal DOPA production (IC50 = 410 and 970 nM for R(-)- and S(+)-apomorphine, respectively). As S(+)-apomorphine but not R(-)-apomorphine is considered to be a dopamine antagonist, these results support the assumption that the block of synaptosomal DOPA production by both apomorphine enantiomers is due to a direct inhibition of tyrosine hydroxylase. Lisuride at high concentrations (10-100 microM) blocked DOPA production in striatal synaptosomes; simultaneously, intrasynaptosomal dopamine was depleted. These data support the assumption that lisuride inhibits DOPA production indirectly, similar to reserpine. In accordance with this assumption, lisuride was without effect on DOPA production in dopamine-depleted synaptosomes. These results demonstrate that inhibition of synaptosomal DOPA production by at least some dopamine agonists may be explained by direct inhibitory effects on tyrosine hydroxylase.
Mol Pharmacol 1985 Dec
PMID:Effects of apomorphine enantiomers and of lisuride on 3,4-dihydroxyphenylalanine production in striatal synaptosomes. 393 8

The steady-state kinetics of tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] frequently exhibits complex features which confound interpretation of the results. Using an assay-enzyme system which is essentially devoid of the major mitigating kinetic features, a comprehensive kinetics data base has been compiled. The studies employed L-tyrosine, 5,6,7,8-tetrahydrobiopterin, and oxygen as substrates, and 3-(3',4'-dihydroxyphenyl)L-alanine, a deazapterin, 3-iodo-L-tyrosine, and dopamine as product, substrate analogue, and product analogue inhibitors, respectively. All three reactants were varied pairwise, and all inhibitors (except dopamine) were tested with each of the three substrates as variable substrate. The entire data base was interpreted exclusively in terms of models for classic saturation kinetics of enzyme catalysis, providing an internally consistent kinetic model and evidence for a sequential mechanism with partially ordered sequences for substrate addition and product release. Some possible mechanisms and experimental variables relating these results to more complex kinetics of tyrosine hydroxylase are considered briefly.
Mol Pharmacol 1983 Jan
PMID:Steady-state kinetics of bovine striatal tyrosine hydroxylase. 613 41

Tyrosine hydroxylase is considered to be the rate-limiting enzyme in the synthesis of catecholamines in both the central and peripheral nervous system. Increased or decreased neuronal activity, stress, lesions, drug effects, endocrinological manipulations and experimental models of hypertension are associated with alterations in tyrosine hydroxylase activity in the central nervous system. In many of these instances, the changes in the activity of tyrosine hydroxylase in the central nervous system that occur are localized to discrete catecholaminergic pathways and nuclei in the brain. The purpose of this review is to summarize and assess this information and to provide insight into the function of catecholamine systems in the brain and their interactions with other putative neurotransmitter systems.
Mol Cell Biochem 1983
PMID:Tyrosine hydroxylase regulation in the central nervous system. 613 60

Incubation of rat pheochromocytoma PC12 cells with 56 mM K+ is associated with increased activity and enhanced phosphorylation of tyrosine hydroxylase in the cells. The increase in the phosphorylation of tyrosine hydroxylase is observed after 30 sec of incubation with 56 mM K+; maximal phosphorylation is observed after 1 min of incubation. In contrast, although a significant increase in the activity of tyrosine hydroxylase is demonstrable after 30 sec of incubation with 56 mM K+, maximal activation is not attained until 3 min of incubation. Both the activation and increased phosphorylation of tyrosine hydroxylase exhibit a similar dependence upon potassium concentration in the incubation medium and are dependent on the presence of extracellular calcium. These results suggest that, although there is a relationship between activation and phosphorylation of tyrosine hydroxylase after potassium-evoked depolarization of rat pheochromocytoma PC12 cells in culture, this relationship may be complex.
Mol Pharmacol 1984 Jul
PMID:Relationship between activation and phosphorylation of tyrosine hydroxylase by 56 mm K+ in PC12 cells in culture. 614 25

At 14 days of age, hypothyroid and normal rats are rendered hypoglycaemic by insulin injection and the subsequent induction in adrenal tyrosine hydroxylase (TH) is studied. Hypothyroidism impairs both the intensity and the time-course of adrenal TH induction.
Mol Cell Endocrinol 1984 Nov
PMID:Tyrosine hydroxylase induction in the young rat: control by thyroid hormones. 615 30

Incubation of primary cultures of chromaffin cells from bovine adrenal medulla with 8-bromo-adenosine 3',5'-monophosphate (8-Br-cyclic AMP) resulted in an increase in proenkephalin mRNA content. The mRNA that increased was detected by hybridization analysis using a cDNA probe and migrated with an apparent size of approximately 1400 bases. The increase in proenkephalin mRNA following 8-Br-cyclic AMP treatment was apparent in 12 hr and continued over 2 days. Corresponding changes were detected in enkephalin-like immunoreactivity but with a 24-hr lag: the cellular content increased significantly after 2 days of treatment and continued to rise over the next 2 days, whereas changes in the amount released to the medium followed the same time course. Dose-response curves for the increase in the content of proenkephalin mRNA and of enkephalin-containing peptides were essentially identical. Chromatographic characterization of the enkephalin-like peptides demonstrated that 8-Br-cyclic AMP increased both the high molecular weight fraction and the low molecular weight fraction, which was shown by high-pressure liquid chromatography to contain Met5-enkephalin, Leu5-enkephalin, and Met5-enkephalin-Arg6-Phe7. Previous results in chromaffin cells have demonstrated that the synthesis of tyrosine hydroxylase is also regulated by cyclic AMP, with a similar time course. These results therefore suggest the possibility of coordinate regulation by cyclic AMP of the expression of the cotransmitters, catecholamines and enkephalin peptides, in the adrenal medulla.
Mol Pharmacol 1984 Sep
PMID:Enkephalin biosynthesis in adrenal medulla. Modulation of proenkephalin mRNA content of cultured chromaffin cells by 8-bromo-adenosine 3',5'-monophosphate. 654 92

Previous work on the rat heart has demonstrated an age-related reduction in catecholamines and a decline in myocardial cell sensitivity to catecholamines in vitro. We used ultrastructural cytochemical techniques to label noradrenergic vesicles of the sympathetic nerve terminals of the rat heart atrium, and addressed the question of whether these deficits are accompanied by a decrease in the number of synaptic vesicles or by progressive axonal degeneration. Our results demonstrate a significant sympathetic axonal degeneration between 3 and 24 months of age. No decrease in noradrenergic vesicle population in the intact nerve terminals could be discerned over this age span. Atrial cell structural alterations observed with age include: (1) increased quantities of residual bodies; (2) infrequent but definite myofibrillar disorganization at cell peripheries; (3) infrequent regional discontinuity of cell attachments and (4) increased extracellular collagen. We suggest that the apparent integrity of noradrenergic vesicle populations is consistent with reports by other investigators that levels of the catecholamine synthesizing enzyme, tyrosine hydroxylase, in sympathetic ganglia increase with age. The previously observed decline in cardiac catecholamines with age may be due to axonal degeneration rather than to reduced noradrenergic vesicles in intact terminals.
J Mol Cell Cardiol 1983 Feb
PMID:An ultrastructural study of the effects of age on sympathetic innervation and atrial tissue in the rat. 685 60

Phospholipase A2 is a calcium-dependent enzyme which produces membrane fusogens. The possibility that it may be involved in exocytosis of catecholamine from primary dissociated cultures of bovine adrenal medullary cells was investigated by studying the effects on catecholamine secretion and 44Ca2+ uptake of three phospholipase A2 inhibitors: p-bromophenacyl bromide (BPB), Upjohn Compound 1002, and mepacrine. The three compounds completely inhibited catecholamine secretion induced by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), elevated K+, and Ba2+. The inhibition of nicotinic agonist-induced secretion by mepacrine may have been caused by direct nicotinic antagonist activity of the drug. The phospholipase inhibitors also inhibited 45Ca2+ uptake into the cells stimulated by DMPP and elevated K+. Inhibition of 45Ca2+ uptake and catecholamine secretion exhibited identical dose-response curves. Other effects of the inhibitors were also investigated. Compound 1002 had no effect on 45Ca2+ efflux from the cells in the presence of either normal or reduced Na+ concentrations. BPB inhibited DMPP-stimulated phosphorylation of tyrosine hydroxylase which, like exocytosis, is dependent on a rise in cytosolic Ca2+. The data suggest that phospholipase A2 inhibitors block catecholamine secretion from intact chromaffin cells by blocking Ca2+ influx.
Mol Pharmacol 1983 May
PMID:Phospholipase A2 inhibitors block catecholamine secretion and calcium uptake in cultured bovine adrenal medullary cells. 686 4


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