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)

Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively as a possible model for the hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR) at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured at 40-microns intervals by a fluorescence microphotometry system in comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels in the medial part of the neostriatum of SHR were lower than those in WKY. We reported previously that the decrease of the serum calcium level in SHR causes a decrease of the dopamine levels in the neostriatum and nucleus accumbens regions through a calmodulin-dependent system, and subsequent low levels of dopamine in the brain which may produce an increase in blood pressure. Combining this finding and our previous reports, we also suggest that the lower dopamine levels seen in the neostriatum and nucleus accumbens regions of SHR may result from the decrease in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to the abnormality of calcium metabolism, and low levels of dopamine may produce an increase in blood pressure through functions of cerebral dopaminergic neurons and peripheral sympathetic nerves.
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PMID:Quantitative immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the brains of spontaneously hypertensive rats. 136 39

Our previous studies suggested that protein kinase C is involved in the veratridine (an activator of voltage-dependent Na+ channels)-induced phosphorylation and activation of tyrosine hydroxylase as well as the synthesis of catecholamines in adrenal medulla (Uezono et al. 1989). In the present study, we investigated whether treatment of cultured bovine adrenal medullary cells with veratridine causes the accumulation of diacylglycerol, a physiological activator of protein kinase C and the translocation of protein kinase C from cytosol to membrane, a process required for protein kinase C activation. Veratridine (100 mumol/l) increased diacylglycerol level about 2.2 fold in a monophasic manner, with peaking at 5 min and declining toward the basal level within 20 min. Veratridine also increased membrane protein kinase C from 15.6% to 26.9% of total protein kinase C in a time-course similar to that of diacylglycerol accumulation. Both stimulatory effects of veratridine were inhibited by tetrodotoxin and not observed in Ca(2+)-free, EGTA-containing medium. Amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchange, did not alter veratridine-induced events. These results suggest that veratridine-induced Ca2+ influx contributes to the accumulation of diacylglycerol and the activation of protein kinase C in adrenal medullary cells.
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PMID:Veratridine causes the Ca(2+)-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medullary cells. 140 8

In order to analyze the feedback action of prolactin (PRL) on the hypothalamus on the cellular level, we used primary cultures of rat embryonic diencephalon to measure the calcium response of individual neurons to PRL by means of fast fluorescence photometry. The cultures were subsequently stained with antibodies against the neuronal marker MAP-2, glutamic acid decarboxylase (GAD) or tyrosine hydroxylase (TH). PRL caused a rapid rise of intracellular free Ca2+ in a specific type of GABAergic neuron characterized by a spindle-shaped bipolar morphology and immunoreactivity to MAP-2 and GAD but not to TH. It is concluded that a subpopulation of hypothalamic GABAergic but not dopaminergic neurons react to PRL with a rapid increase in intracellular free Ca2+. These data are compatible with the assumption of a rapid negative feedback regulation of the secretion of PRL from the pituitary mediated by tuberoinfundibular GABAergic neurons.
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PMID:Diencephalic GABAergic neurons in vitro respond to prolactin with a rapid increase in intracellular free calcium. 140 68

The effects of exogenous GM1 ganglioside on depolarization and ligand-induced Ca2+ signaling were investigated in PC12 cells. Cellular responses to K+ depolarization and bradykinin application in control and GM1-treated cells were examined with respect to: 1) changes in the intracellular Ca2+ concentration ([Ca2+]i) measured using fura-2 fluorescence in single cells, and 2) changes in Ca(2+)-dependent protein kinase activity as assayed by two-dimensional phosphopeptide analysis of the site-specific phosphorylation of tyrosine hydroxylase. Pretreatment of cells with GM1 (10 or 100 microM) enhanced K+ depolarization-stimulated increases in [Ca2+]i and in 32PO4 incorporation into tyrosine hydroxylase phosphopeptide T2, a Ca2+/calmodulin-dependent protein kinase II substrate. In contrast, GM1 treatment had no effect on the transient increases in [Ca2+]i evoked by bradykinin or on bradykinin-induced increases in the site-specific phosphorylation of tyrosine hydroxylase. The depolarization-induced and GM1-enhanced increases in [Ca2+]i and T2 phosphorylation were prevented by removal of external Ca2+ or pretreatment with 1 microM nitrendipine, suggesting that these increases result from Ca2+ entry through dihydropyridine-sensitive Ca2+ channels. The ability of exogenous gangliosides to potentiate increases in [Ca2+]i may underlie their diverse neuritogenic and neurotrophic actions in the nervous system.
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PMID:Modulation of a Ca2+ signaling pathway by GM1 ganglioside in PC12 cells. 144 16

1. Two sub-populations of pars compacta substantia nigra neurones were identified with very different electrophysiological properties and rostral-caudal distribution. Both cell types were identified by biocytin intracellular dye injection and found to be located within pars compacta containing tyrosine hydroxylase-positive cells. These sub-populations displayed distinctly different responses to transient anoxia. 2. The first group ('Phasic' neurones) exhibited a low threshold calcium conductance LTS gCa associated with bursts of action potentials, were located at the level of the mammillary bodies and were highly sensitive to anoxia. The second group ('rhythmic' neurones) fired in a rhythmic pattern, were located at the level of the accessory optic tract and were relatively insensitive to anoxia. 3. The anoxic response of phasic cells was characterized by membrane hyperpolarization (mean 12 mV), a decrease in input resistance (mean 36%) and cessation of action potential firing. The axonic response of these neurones was not blocked by TEA (5-10 mM), haloperidol (100 microM), the removal of extracellular calcium or depletion of endogenous dopamine. However, this effect was blocked by both the sulphonylurea tolbutamide (50-500 microM), and also by quinine (100 microM) and could be mimicked by application of diazoxide (1 mM). 4. Rhythmic cells displayed a variable response to anoxia consisting of either modest depolarization, hyperpolarization or no change in membrane potential, in all cases accompanied by little or no change in input resistance. The polarity of the membrane potential shift during anoxia was reversed by TEA (5-10 mM) or the removal of calcium. These cells were also relatively insensitive to diazoxide (1 mM). 5. It is concluded from the neuronal responses to anoxia and the pharmacological modification of these responses, that the ATP-sensitive potassium channel (KATP channel) is functionally operative in the substantia nigra and is primarily distributed on the phasically discharging cells of the rostral pars compacta. The relevance of this recently discovered ionic channel is discussed with regard to the normal and abnormal functioning of the substantia nigra.
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PMID:Neuronal selectivity of ATP-sensitive potassium channels in guinea-pig substantia nigra revealed by responses to anoxia. 146 28

The overflows of 3,4-dihydroxyphenylalanine, dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol in canine portal vein superfused in vitro were studied before, during, and after depolarization of sympathetic nerve endings. The four compounds were separated from superfusate and from tissue on Sep-Pak C-18 cartridges and quantified by HPLC with electrochemical detection. Physiological and biochemical methods were used to show that the compound released was most probably 3,4-dihydroxyphenylalanine; the identity of the other endogenous compounds has been established previously. Release of 3,4-dihydroxyphenylalanine was calcium and frequency dependent, inhibited by a-m-L-p-tyrosine (an inhibitor of tyrosine hydroxylase) and augmented by 3-hydroxybenzylhydrazine (an inhibitor of aromatic amino acid decarboxylase). The overflows of dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol from the vein were calcium and frequency dependent. It was estimated that under control conditions, approximately 80% of the total 3,4-dihydroxyphenylalanine that was synthesized was directed to catecholamine biosynthesis, approximately 8% overflowed from the vein, and approximately 14% remained unchanged within the tissue. It is concluded that 3,4-dihydroxyphenylalanine and dopamine are released together with noradrenaline and 3,4-dihydroxyphenylglycol from portal vein upon nerve depolarization.
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PMID:Dihydroxyphenylalanine and dopamine are released from portal vein together with noradrenaline and dihydroxyphenylglycol during nerve stimulation. 149 20

The lymphatic vessels conduct lymph fluid, proteins, and potentially antigenic material from the interstitium back to the bloodstream via lymph nodes, where solids are removed by phagocytic cells and recirculating lymphocytes and immunoglobulins are added. Immunostaining for two general neuronal markers, protein gene product 9.5 (PGP 9.5), a cytoplasmic ubiquitin C-terminal hydrolase, and synaptophysin, a calcium-binding four-span integral synaptic vesicle membrane glycoprotein, disclosed an abundant innervation of the large femoral lymphatic vessels in rats. This confirms and extends earlier findings based on nonspecific intravital methylene blue and silver impregnation staining methods. Nerves containing neuropeptide Y, C-flanking peptide of neuropeptide Y, and tyrosine hydroxylase, markers of noradrenergic postganglionic sympathetic fibers, were frequent whereas immunoreactivity to vasoactive intestinal peptide, a neuropeptide present in many cholinergic parasympathetic nerve fibers, was sparse suggesting possible sympathetic and parasympathetic influences. Furthermore, calcitonin gene-related peptide- and substance P-containing fibers were also present in the walls of lymphatic vessels suggesting a possible sensory influence in the coordinated myogenic responses. By comparison to normal light microscopy, confocal microscopy was found useful to trace the perihilar penetration of blood and afferent lymphatic vessels in lymph nodes. PGP 9.5-immunoreactive fibers were found in and around lymph nodes suggesting that there is a neural regulation of lymphoid node function. Because of their distribution, peptide-containing nerves may participate in regulating the capacity of the lymphatic pumping activity, and may possibly exert paracrine effects on lymphocytes.
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PMID:Peptide-containing innervation of rat femoral lymphatic vessels. 160 41

Changes induced by internal administration of L-tyrosine and L-phenylalanine in high-threshold calcium currents have been studied on perfused PC12 pheochromocytoma cells using whole-cell voltage-clamp technique. A method for rapid changes of perfusing solutions has been used. L-Tyrosine (20 microM) slowed down the decline ('wash-out') of ICa occurring during intracellular perfusion and in most cells induced its temporary recovery. alpha-Methyl-D,L-tyrosine (a tyrosine hydroxylase blocker) exerted a similar effect. On the other hand, L-phenylalanine (20 microM) in most cells speeded-up the decline of ICa. Replacement of ATP in the perfusing solution by an equivalent amount of ADP (2 mM) did not alter the effects of amino acids. The possible mechanisms of the described changes are discussed in connection with the known role of L-tyrosine in posttranslational modifications of microtubular proteins.
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PMID:Effects of intracellular administration of L-tyrosine and L-phenylalanine on voltage-operated calcium conductance in PC12 pheochromocytoma cells. 165 34

We reported that one of the isoquinolinesulfonamide derivatives, KN-62, is a potent and specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) (Tokumitsu, H., Chijiwa, T., Hagiwara, M., Mizutani, A., Terasawa, M. and Hidaka, H. (1990) J. Biol. Chem. 265, 4315-4320). We have now investigated the inhibitory property of a newly synthesized methoxybenzenesulfonamide, KN-93, on CaMKII activity in situ and in vitro. KN-93 elicited potent inhibitory effects on CaMKII phosphorylating activity with an inhibition constant of 0.37 microM but this compound had no significant effects on the catalytic activity of cAMP-dependent protein kinase, Ca2+/phospholipid dependent protein kinase, myosin light chain kinase and Ca(2+)-phosphodiesterase. KN-93 also inhibited the autophosphorylation of both the alpha- and beta-subunits of CaMKII. Kinetic analysis indicated that KN-93 inhibits CaMKII, in a competitive fashion against calmodulin. To evaluate the regulatory role of CaMKII on catecholamine metabolism, we examined the effect of KN-93 on dopamine (DA) levels in PC12h cells. The DA levels decreased in the presence of KN-93. Further, the tyrosine hydroxylase (TH) phosphorylation induced by KCl or acetylcholine was significantly suppressed by KN-93 in PC12h cells while events induced by forskolin or 8-Br-cAMP were not affected. These results suggest that KN-93 inhibits DA formation by modulating the reaction rate of TH to reduce the Ca(2+)-mediated phosphorylation levels of the TH molecule.
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PMID:The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. 166 7

Increased Ca2+ influx serves as a signal that initiates multiple biochemical and physiological events in neurons following depolarization. The most widely studied of these phenomena is the release of neurotransmitters. In sympathetic neurons, depolarization also increases the rate of synthesis of the transmitter norepinephrine (NE), via an activation of the enzyme tyrosine hydroxylase (TH), and this effect also seems to involve Ca2+ entry. We have examined whether the mechanism of Ca2+ entry relevant to TH activation is via voltage-sensitive Ca2+ channels and, if so, whether the type of Ca2+ channel involved is the same as that involved in the stimulation of NE release. We have investigated the isolated rat iris, allowing us to examine transmitter biosynthesis and release in sympathetic nerve terminals in the absence of sympathetic cell bodies and dendrites. Potassium depolarization produced a three- to fivefold increase in TH activity and an approximately 100-fold increase in NE release. Both effects were dependent on Ca2+ being present in the extracellular medium, and both were inhibited by omega-conotoxin (1 microM), which inhibits N-type voltage-sensitive Ca2+ channels. In contrast, the dihydropyridine nimodipine (1-3 microM), which blocks L-type Ca2+ channels, had no effect on either measure. These data support the hypothesis that increases in NE biosynthesis and release in sympathetic nerve terminals during periods of depolarization are both initiated by an influx of Ca2+ through voltage-sensitive Ca2+ channels and that a similar type of Ca2+ channel is involved in both processes.
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PMID:Omega-conotoxin inhibits the acute activation of tyrosine hydroxylase and the stimulation of norepinephrine release by potassium depolarization of sympathetic nerve endings. 167 Oct 89


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