Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
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A light microscope study using postembedding immunocytochemistry techniques to demonstrate the common neurotransmitter candidates gamma-aminobutyric acid (GABA), glycine, glutamate, and tyrosine hydroxylase for dopamine has been done on human retina. By using an antiserum to GABA, we found GABA-immunoreactivity (GABA-IR) to be primarily in amacrine cells lying in the inner nuclear layer (INL) or displaced to the ganglion cell layer (GCL). A few stained cells in the INL, which are probably interplexiform cells, were observed to project thin processes towards the outer plexiform layer (OPL). There were heavily stained bands of immunoreactivity in strata 1, 3 and 5 of the inner plexiform layer (IPL). An occasional ganglion cell was also GABA-IR. By using an antiserum to glycine, stained cells were observed at all levels of the INL. Most of these were amacrines, but a few bipolar cells were also glycine-IR. Displaced amacrine cells and large-bodied cells, which are probably ganglion cells, stained in the GCL. The bipolar cells that stained appeared to include both diffuse and midget varieties. The AII amacrine cell of the rod pathway was clearly stained in our material but at a lower intensity than two other amacrine cell types tentatively identified as A8 and A3 or A4. Again, there was stratified staining in the IPL, with strata 2 and 4 being most immunoreactive. An antiserum to glutamate revealed that most of the neurons of the vertical pathways in the human retina were glutamate-IR. Rod and cone photoreceptor synaptic endings labeled as did the majority of bipolar and ganglion cells. The rod photoreceptor stained more heavily than the cone photoreceptor in our material. While both midget and diffuse cone bipolar cell types were clearly glutamate-IR, rod bipolars were not noticeably stained. The most strongly staining glutamate-IR processes of the IPL lay in the outer half, in sublamina a. The antiserum to tyrosine hydroxylase (TOH) revealed two different amacrine cell types. Strongly immunoreactive cells (TOH1) had their cell bodies in the INL and their dendrites ramified in a dense plexus in stratum 1 of the IPL. Fine processes arising from their cell bodies or from the stratum 1 plexus passed through the INL to reach the OPL but did not produce long-ranging ramifications therein. The less immunoreactive amacrines (TOH2) lay in the INL, the center of the IPL or the GCL and emitted thick dendrites that were monostratified in stratum 3 of the IPL.
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PMID:Localization of GABA, glycine, glutamate and tyrosine hydroxylase in the human retina. 134 92

Postembedding electron microscope immunocytochemistry of glycine and GABA conjugated to colloidal gold has been applied to pre-embedded cat retina stained with the antibody against tyrosine hydroxylase (Toh+). Toh+ stained cells are the equivalent of A18 amacrine cells of Golgi descriptions (Kolb et al., '81). The dendrites of Toh+ cells synapse upon several different types of glycine-positive amacrine cell bodies. We suggest that these are the A8, A3/A4, and AII amacrine cell varieties by analogous immunocytochemical staining intensity, to glycine autoradiographic labeling intensity (Pourcho and Goebel, '85). The greatest number of synapses from Toh+ dendrites are directed at the least glycine-positive amacrine, which is the AII cell by all morphological criteria. A few glycine-positive profiles are also presynapatic to the Toh+ stained cell body itself. Toh+ profiles are also presynaptic to GABA-positive amacrine cell bodies. The commonest amacrine synapsed upon is very heavily labeled with GABA immunocytochemistry. We consider it to be the A17 amacrine cell, which is known to label strongly by [3H] muscimol autoradiography (Pourcho and Goebel, '83). The cell body of the Toh+ amacrine cell also receives many synapses, which appear to be GABA-positive, and Toh+ profiles running in stratum 1 of the inner plexiform layer (IPL) are both pre- and postsynaptic to GABA-positive amacrine cell profiles. In addition, the cell body and primary dendrites of the Toh+ cell receive input from a bipolar type and GABA- or glycine-negative profiles. GABA-positive profiles, belonging to the interplexiform cell (IPC), are synapsed upon by Toh+ profiles that run in the outer plexiform layer (OPL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postembedding immunocytochemistry for GABA and glycine reveals the synaptic relationships of the dopaminergic amacrine cell of the cat retina. 172 Jan 42

The purpose of this study was to examine the effects of angiotensin on the enzyme activities and gene expression of two catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT), in bovine adrenal medullary (AM) cells. Short term (15 min) incubation of cultured AM cells with 2 nM [Sar1]angiotensin II (s1-AII) did not increase basal secretion of catecholamines; however, longer incubations (3, 24, or 72 h) produced 4-10-fold increases. To determine whether angiotensin affects synthesis of catecholamines, the activities of TH and PNMT were examined. Incubation with s1-AII (15-30 min) decreased the Km of TH for its biopterine cofactor [6R)-5,6,7,8-tetrahydro-1-biopterin dihydrochloride (BH4] without affecting the Vmax, suggesting activation of TH. After long term incubation (72 h) the Km value was identical to that of control, while increases in the apparent Vmax were observed. PNMT activity was unaffected during a 30-min treatment with s1-AII; however, 2-fold increases occurred after a 48-72-h incubation. s1-AII (24 h) increased the relative abundance of TH and PNMT mRNAs, suggesting that the long term increase in enzyme activities reflected increased expression of TH and PNMT genes. Maximal increases were observed at 2 nM s1-AII and the changes were antagonized by saralasin. Induction of TH mRNA by s1-AII was additive to the effects of veratridine or forskolin indicating that effects of angiotensin were not due to membrane depolarization or increased cyclic AMP levels. Incubation with Ca2+ ionophore A23187 increased TH and PNMT mRNA levels in AM cells raising the possibility that the increase in cellular [Ca2+] could mediate effects of angiotensin. Angiotensin-induced increases in TH and PNMT mRNA were inhibited by nifedipine indicating involvement of voltage-dependent Ca2+ channels. In addition, the increases in TH, but not PNMT mRNA, were antagonized by dantrolene, which inhibits mobilization of Ca2+ from intracellular stores. Calmodulin involvement was suggested by the inhibition of s1-AII induced changes in mRNA with 1 microM calmidazolium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Short and long term regulation of catecholamine biosynthetic enzymes by angiotensin in cultured adrenal medullary cells. Molecular mechanisms and nature of second messenger systems. 196 64

The dopaminergic amacrine cells of the cat retina have been stained by immunocytochemistry using an antibody to tyrosine hydroxylase (Toh). The complete population of Toh+ cells has been studied by light microscopy of retinal wholemounts to evaluate morphological details of dendritic structure and branching patterns. Selected Toh+ amacrine cells have been studied by serial-section electron microscopy to analyse synaptic input and output relationships. The majority of Toh+ amacrine cells occur in the amacrine cell layer of the retina and have their dendrites ramifying and forming the characteristic rings in stratum 1 of the inner plexiform layer. A minority of Toh+ cells have cell bodies displaced to the ganglion cell layer but their dendrites also stratify in stratum 1. All Toh+ cells have some dendritic branches running in stratum 2 as well as in stratum 1, and frequently they have long 'axon-like' processes (500-1000 microns long) dipping down to run in stratum 5 before passing up to rejoin the major dendritic arbors in stratum 1. In addition Toh+ stained processes follow blood vessels in the inner plexiform layer and in the ganglion cell layer. A population of Toh+ cells found in the inferior retina appears to give rise to stained processes that pass to the outer plexiform layer and therein to run for as far as one millimeter. Electron microscopy reveals that Toh+ amacrine cells are postsynaptic to amacrine cells and a few bipolar cell terminals in stratum 1 of the inner plexiform layer and are primarily presynaptic to AII amacrine cell bodies and lobular appendages, and to another type of amacrine cell body and amacrine dendrites hypothesized to be the A17 amacrine cell. The Toh+ dendrites in stratum 2 are presynaptic to AII lobular appendages primarily. Stained 'axon-like' processes running in stratum 5 prove to be presynaptic to AII amacrine dendrites as they approach the rod bipolar axon terminals and they may also be presynaptic to the rod bipolar terminal itself. The Toh+ stained dendrites that have been followed in the outer plexiform layer run along the top of the B-type horizontal cell somata and may have small synapses upon them. The only clear synapses seen in the outer plexiform layer are from the Toh+ profiles upon vesicle filled amacrine-like profiles that are in turn presynaptic to bipolar cell dendrites in the outer plexiform layer. We presume the cells postsynaptic to the Toh+ dendrites in the outer plexiform layer are interplexiform cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The synaptic organization of the dopaminergic amacrine cell in the cat retina. 239 38

Parvalbumin (PV) is a calcium-binding protein localized to selected neurons in the nervous system, including the retina. This investigation evaluated the distribution of PV immunoreactivity in the rabbit retina using immunohistochemistry with a monoclonal antibody directed to carp PV. In the inner nuclear layer (INL), PV immunoreactivity was present in horizontal and amacrine cells. In the ganglion cell layer, PV immunostaining was confined to somata that are likely to be both displaced amacrine cells and ganglion cells. PV-immunoreactive (IR) amacrine cells were positioned in the proximal INL adjacent to the inner plexiform layer (IPL). These cells usually gave rise to a single primary process, which arborized into two distinct bands in the IPL. In sublamina a, the processes were thin and had large, irregular endings. In sublamina b, multiple processes branched from the primary process and were characterized by varicosities and spines. PV-IR amacrine cell bodies measured from 8 to 10 microns in diameter. Their density was highest in the visual streak and lowest in the periphery of the superior retina. The average number of PV-IR amacrine cells was 464,045 cells per retina (N = 3), and the average regularity index of the PV-IR cell mosaic was 3.23. PV-IR amacrine cells were further characterized by double-label immunofluorescence experiments using antibodies to PV and tyrosine hydroxylase (TH). Varicose TH-IR processes were in close apposition to many PV-IR amacrine cells and often formed "ring structures" around them. Together, these morphological, quantitative, and histochemical observations indicate that PV immunoreactivity in the INL is localized predominantly to AII amacrine cells, and therefore it is a valuable marker for the identification of this cell type.
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PMID:AII amacrine cell population in the rabbit retina: identification by parvalbumin immunoreactivity. 762 7

In the rabbit retina, parvalbumin has been localized selectively to AII amacrine cells, while 28 kDa calbindin could be detected in horizontal cells, in one type of depolarizing cone bipolar cell and a population of wide-field amacrine cells. The distribution of the third neuronal calcium binding protein, calretinin, however, has not been studied to date in detail in the rabbit retina. Therefore in this study we aimed to describe the overall distribution of calretinin in the different retinal layers and the possible colocalization pattern with other neurochemical marker molecules. A few cone photoreceptor cells were found to be labeled, whereas the outer plexiform layer was free from immunoreactive elements. In the most proximal row of the inner nuclear layer amacrine cells were labeled, while more distally a few cells emitted beaded axon-like processes toward the outer retina. There were large (18-28 microm in diameter) cells labeled in the ganglion cell layer, of which many apparently had their axon stained. Some of the calretinin immunoreactive amacrine cells (the AII neurons) also contained parvalbumin. Colocalization of calretinin and 28 kDa calbindin could not be ascertained in the same amacrine cell populations, nor was tyrosine hydroxylase present in calretinin-containing cells. There was partial colocalization of calretinin in the gamma-aminobutyric acid-positive amacrine cell population. Parvalbumin containing ganglion cells were also positive for calretinin; however, the calretinin-positive ganglion cells were more numerous. gamma-Aminobutyric acid could be colocalized in some calretinin-positive neurons of the ganglion cell layer.
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PMID:Calretinin in neurochemically well-defined cell populations of rabbit retina. 927 31

Caldendrin is a novel calcium-binding protein confined to the somatodendritic compartment of neurons. Here we have studied the expression pattern of caldendrin in the rat retina. First we assessed the distribution of caldendrin transcripts in the adult and developing retina by in situ hybridization. In the adult retina, transcripts are expressed mainly in the inner half of the inner nuclear layer (INL) and to a lesser extent in the ganglion cell layer (GCL). During development labeling of the inner part of the cytoblast layer, where amacrine cells reside, is already present at postnatal day 1 (P1). The intensity of hybridization signal in this sublamina of the developing INL increases up to P8, whereas significant labeling in the GCL was first found at P14, coinciding with eye opening. Immunodetection with a polyclonal antibody revealed intensive staining of cells in the inner retina, which are presumably mainly amacrine and significantly fewer bipolar and ganglion cells. All parvalbumin-containing All amacrines were immunopositive for caldendrin. Colocalization with calbindin was found in cone bipolar cells, the majority of AII amacrines, and calbindin-positive cells in the GCL. In the GCL, caldendrin was also colocalized with calretinin-immunopositive cells. Most caldendrin-positive amacrine cells in the adult rat retina were glycinergic and only a few were GABAergic. In retinal flat mounts, it was confirmed that less than 10% of retrogradely labeled retinal ganglion cells (RGC) are caldendrin-positive. Caldendrin immunoreactivity does not colocalize with tyrosine hydroxylase, VIP, substance P and somatostatin immunoreactivity. In summary, caldendrin expression is regulated differentially in retinal cell types during development and is restricted to a subpopulation of amacrine, bipolar, and ganglion cells, suggesting specific functions in the developing and mature retina.
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PMID:The cytoskeleton-associated neuronal calcium-binding protein caldendrin is expressed in a subset of amacrine, bipolar and ganglion cells of the rat retina. 1055 36

The morphology of calretinin- and tyrosine hydroxylase-immunoreactive (IR) neurons in adult pig retina was studied. These neurons were identified using antibody immunocytochemistry. Calretinin immunoreactivity was found in numerous cell bodies in the ganglion cell layer. Large ganglion cells, however, were not labeled. In the inner nuclear layer, the regular distribution of calretinin-IR neurons, the inner marginal location of their cell bodies in the inner nuclear layer, and the distinctive bilaminar morphologies of their dendritic arbors in the inner plexiform layer suggested that these calretinin-IR cells were AII amacrine cells. Calretinin immunoreactivity was observed in both A-and B-type horizontal cells. Neurons in the photoreceptor cell layer were not labeled by this antibody. The great majority of tyrosine hydroxylase-IR neurons were located at the innermost border of the inner nuclear layer (conventional amacrines). The processes were monostratified and ran laterally within layer 1 of the inner plexiform layer. Some of the tyrosine hydroxylase-IR neurons were located in the ganglion cell layer (displaced amacrines). The processes of displaced tyrosine hydroxylase-IR amacrine cells were also located within layer 1 of the inner plexiform layer. Some processes of a few neurons were located in the outer plexiform layer. A very low density of neurons had additional bands of tyrosine hydroxylase-IR processes in the middle and deep layers of the inner plexiform layer. The processes of tyrosine hydroxylase-IR neurons extended radially over a wide area and formed large, moderately branched dendritic fields. These processes occasionally had varicosities and formed "dendritic rings". These results indicate that calretinin- and tyrosine hydroxylase-IR neurons represent specific neuronal cell types in the pig retina.
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PMID:Morphology of calretinin and tyrosine hydroxylase-immunoreactive neurons in the pig retina. 1135 8

Angiotensin II (AII, 100 nM) stimulation of bovine adrenal chromaffin cells (BACCs) produced angiotensin II receptor subtype 1 (AT1)-mediated increases in extracellular regulated protein kinase 1/2 (ERK1/2) and stress-activated p38MAPK (p38 kinase) phosphorylation over a period of 10 min. ERK1/2 and p38 kinase phosphorylation preceded Ser31 phosphorylation on tyrosine hydroxylase (TOH). The inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) activation, PD98059 (0.1-50 microM) and UO126 (0.1-10 microM), dose-dependently inhibited both ERK2 and Ser31 phosphorylation on TOH in response to AII, suggesting MEK1/2 involvement. The p38 kinase inhibitor SB203580 (20 microM, 30 min) abolished Ser31 and Ser19 phosphorylation on TOH and partially inhibited ERK2 phosphorylation produced by AII. In contrast, 1 microM SB203580 did not affect AII-stimulated TOH phosphorylation, but fully inhibited heat shock protein 27 (HSP27) phosphorylation produced by AII. Also, 1 microM SB203580 fully inhibited Ser19 phosphorylation on TOH and HSP27 phosphorylation in response to anisomycin (30 min, 10 microg/mL). The results suggest that ERKs mediate Ser31 phosphorylation on TOH in response to AII, but p38 kinase is not involved. Previous studies suggesting a role for p38 kinase in the phosphorylation of Ser31 are explained by the non-specific effects of 20 microM SB203580 in BACCs. The p38 kinase pathway is able to phosphorylate Ser19 on TOH in response to anisomycin, but does not do so in response to AII.
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PMID:Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells: the role of MAPKs after angiotensin II stimulation. 1148 51

Substance P is the preferred ligand for the neurokinin 1 (NK1) receptor. In vertebrate retinas, substance P is expressed by amacrine, interplexiform and ganglion cells. Substance P influences the activity of amacrine and ganglion cells and it is reported to evoke dopamine release. We investigated NK1 receptor expression in the rabbit retina using affinity-purified NK1 receptor antibodies. NK1 receptors were expressed by two distinct populations of retinal neurons. One is a population of ON-type bipolar cells characterized by axonal arborizations that ramified in the inner plexiform layer near the ganglion cell layer. Double-label studies showed that NK1 receptor-expressing bipolar cells were distinct from rod bipolar cells and from other immunocytochemically identified types of cone bipolar cells. Their density was about 2250 cells/mm2 in the visual streak and 1115 cells/mm2 in ventral mid-periphery. They were distributed in a non-random pattern. In the outer plexiform layer, the dendrites of these bipolar cells converged into heavily immunostained clusters having a punctate appearance. The density of these clusters in mid-peripheral ventral regions (about 13000 clusters/mm2) was similar to the reported cone density [Famiglietti and Sharpe (1995) Vis. Neurosci. 12, 1151-1175], suggesting these dendrites contact all cone photoreceptors. The second NK1 receptor expressing cell population corresponds to the tyrosine hydroxylase-containing amacrine cell population. NK1 receptor immunostaining was localized to the cell body and processes, but not to the processes that form the 'rings' that are known to encircle somata of AII amacrine cells. These findings show that NK1 receptor immunoreactivity is localized to a population of ON-type cone bipolar cells and to dopaminergic amacrine cells, suggesting that substance P acting on NK1 receptors influences multiple retinal circuits in the rabbit retina.
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PMID:Expression of the neurokinin 1 receptor in the rabbit retina. 1245 99


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