Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrophysiological properties and opioid responsiveness of the dopamine-containing neurons in the arcuate nucleus of the guinea pig hypothalamus were examined. Dopamine-containing neurons, identified immunocytochemically by the presence of tyrosine hydroxylase, had a mean length-to-width profile of 14.9 +/- 4.4 x 11.5 +/- 3.1 microns (N = 14). The Na+ action potential of these neurons was of short duration, and induction of repetitive firing (20-50 Hz) caused an afterhyperpolarization of 6-9 mV in amplitude, with a decay half-time of approximately 1.5 sec. Dopamine-containing cells exhibited a low threshold spike, which induced 1-4 Na+ action potentials. This potential had a threshold close to -65 mV, could not be induced without prior hyperpolarization and was not sensitive to TTX. Dopamine-containing neurons also exhibited a time- and voltage-dependent inward current at potentials negative to -70 mV, and Cs+ blocked this conductance. The mu-opioid agonist Tyr-D-Ala-Gly-mePhe-Gly-ol hyperpolarized (14 +/- 3 mV) dopamine neurons via induction of an outward current (93 +/- 44 pA near the resting membrane potential) which had a reversal potential similar to that expected for a selective potassium conductance. TTX (1 microM) did not block the opioid effects. These results show that dopamine neurons of the arcuate nucleus differ in their intrinsic conductances and their responsiveness to opioids from other CNS dopaminergic neurons. Furthermore, opioid activation of a potassium conductance resulted in a direct hyperpolarization of dopamine neurons of the arcuate nucleus, and we suggest that this mechanism may underlie the effects of opioids on dopamine-mediated prolactin release.
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PMID:Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus. 197 95

We have previously shown that stimulation of the preganglionic cervical sympathetic trunk leads to an acute increase in tyrosine hydroxylase (TyrOHase) activity in the rat superior cervical ganglion. This increase appears to be mediated in part by acetylcholine and in part by a second neurotransmitter. As a first step in an attempt to determine the identity of this noncholinergic transmitter, we have examined the ability of a number of neuropeptides to increase ganglionic TyrOHase activity in vitro. Secretin and vasoactive intestinal peptide (VIP) both stimulated TyrOHase activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, glucagon, insulin, luteinizing hormone-releasing hormone, [D-Ala(2), Met(5)]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin produced a significant increase in TyrOHase activity at 1 nM and a maximal elevation at 0.1 muM. VIP produced a significant increase at 0.1 muM and a near maximal effect at 10 muM. Although secretin was about 2 orders of magnitude more potent than VIP, it produced a significantly smaller maximal increase in enzyme activity. Incubation of ganglia with both secretin (10 muM) and VIP (10 muM) produced an increase in TyrOHase activity that was not significantly different from that produced by VIP alone. The stimulatory effects of secretin and VIP were reversible within minutes after removal of the peptides. Neither incubation of intact ganglia with the cholinergic antagonists hexamethonium and atropine nor prior decentralization of ganglia altered the response to the peptides. Thus, the data demonstrate that secretin and VIP acutely increase TyrOHase activity in the superior cervical ganglion and suggest that they produce this effect by acting directly on ganglionic neurons. It remains to be determined whether secretin or VIP or a related peptide is released during preganglionic nerve firing and whether one or more of these peptides is responsible for the noncholinergic elevation of TyrOHase activity produced by preganglionic nerve stimulation.
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PMID:Secretin and vasoactive intestinal peptide acutely increase tyrosine 3-monooxygenase in the rat superior cervical ganglion. 613 May 26

Several lines of evidence indicate that an interaction exists between opioid peptides and midbrain dopaminergic neurons. The purpose of this study was to map and quantify the density of the mu opioid receptor subtype relative to the location of the dopaminergic (DA) neurons in the retrorubral field (nucleus A8), substantia nigra (nucleus A9), and ventral tegmental area and related nuclei (nucleus A10) in the rat. Sections through the rostral-caudal extent of the midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the mu-selective ligand, 3H-Tyr-D-Ala-N-MePhe-Gyl-ol enkephalin. In the nucleus A8 region, there were low levels of mu binding. In the rostral portion of nucleus A9, there was prominent mu binding both in the ventral pars compacta, which contains numerous DA neurons, and in regions that correspond to the location of the DA dendrites which project ventrally into the underlying substantia nigra pars reticulata. In the caudal portion of nucleus A9, mu binding was greatest in the substantia nigra pars reticulata, but also in the same region that contains DA neurons. In nucleus A10, mu receptor densities differed depending upon the nucleus A10 subdivision, and the rostral-caudal position in the nucleus. Low receptor densities were observed in rostral portions of the ventral tegmental area and interfascicular nucleus, and there was negligible binding in the parabrachial pigmented nucleus and paranigral nucleus at the level of the interpeduncular nucleus; all regions where there are high densities of DA somata. Mu binding was relatively high in the central linear nucleus, and in the dorsal and medial divisions of the medial terminal nucleus of the accessory optic system, which has been shown to contain DA dendrites. These data indicate that mu opioid receptors are located in certain regions occupied by all three midbrain DA nuclei, but in a highly heterogeneous fashion.
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PMID:Opioid receptors in midbrain dopaminergic regions of the rat. I. Mu receptor autoradiography. 838 84

Using a specific antiserum recently raised against [D-Ala2]deltorphin I (DADTI: Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2), a highly selective ligand for delta-opioid receptors, we have previously demonstrated the occurrence of positive immunostaining in several structures of mouse brain. We describe here the neuroanatomical distribution patterns of DADTI-immunoreactive neuronal bodies, axons, and tanycytes in rat brain. Positive neuronal somata were localized mainly in the ventral mesencephalon, including the ventral tegmental area and the pars compacta of the substantia nigra. A minor population of positive somata was found in the pars reticulata and pars lateralis of the substantia nigra, raphe nuclei, supramammillary nucleus, and retrorubral reticular nucleus. All these regions, except for the supramammillary nucleus, contain dopamine cell bodies. Intensely stained positive nerve fibers could be traced along the medial forebrain bundle. Dense positive terminals were seen in the neostriatum, nucleus accumbens shell, olfactory tubercle, septal areas, cingulate, and medial prefrontal cortex. Double-immunostaining study revealed that, in the substantia nigra, almost all (97.8%) DADTI-positive neurons colocalized with tyrosine hydroxylase (TH), and the doubly stained cells occupied about one-third (29.1%) of the total population of TH-positive neurons. Only a few DADTI/TH-positive cells also stained for 28-kDa calbindin D, although many neurons double-stained for 28-kDa calbindin D and TH. In contrast, the supramammillary nucleus contained a number of DADTI-positive cells, which nearly always stained positively for 28-kDa calbindin D but did not stain for TH. The association of DADTI-like immunoreactivity with certain dopaminergic pathways seems of particular interest. A small population of DADTI-immunostained tanycytes was present in the ventral part of the third ventricle wall.
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PMID:[d-Ala2]deltorphin I-like immunoreactivity in the adult rat brain: immunohistochemical localization. 841 53

A major problem in neural transplantation therapy is poor survival of grafted cells, which may be due to low cell viability prior to transplantation or scarce trophic factors available to the cells following transplantation. Recently, the delta enkephalin analogue [D-Ala(2),D-Leu(5)]-enkephalin (DADLE) has been demonstrated to protect against, as well as to reverse methamphetamine-induced loss of dopamine transporters. Here, we show that pretreatment with DADLE (0.0025, 0.005, 0.01 g/ml) dose-dependently enhanced cell viability of cultured primary rat fetal mesencephalic cells. In addition, DADLE administration in adult rats (4 mg/kg every 2 h, 4 injections, i.p.) prior to 6-hydroxydopamine lesions of the medial forebrain bundle, significantly reduced the severity of loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra 1 month post-lesion. This is the first report suggesting that DADLE can be used as a supplement factor for improving the cell viability of fetal mesencephalic cells and as a protective agent against neurotoxicity in a Parkinson's disease model.
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PMID:Treatment with delta opioid peptide enhances in vitro and in vivo survival of rat dopaminergic neurons. 1079 Aug 56

[D-Ala(2), D-Leu(5)]enkephalin (DADLE) has been previously reported to prolong the survival of tissues both in the periphery and in the central nervous system. Here, we show that DADLE was able to block the protein as well as the functional loss of dopamine transporter (DAT) and tyrosine hydroxylase (TH) induced by methamphetamine. Male CD-1 mice received four injections of methamphetamine (10 mg/kg, i.p. ) at 2-h intervals. DADLE (4 mg/kg, i.p.) was given 30 min before each injection of methamphetamine. Western blotting and enzymatic assays showed that DADLE blocked the protein loss and functional impairment of DAT and TH induced by methamphetamine.
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PMID:Blockade of dopamine transporter and tyrosine hydroxylase activity loss by [D-Ala(2), D-Leu(5)]enkephalin in methamphetamine-treated CD-1 mice. 1098 Feb 66

Delta enkephalin analogue [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to protect dopamine transporters from methamphetamine-induced neurotoxicity. In the present study, we demonstrate that exposure of embryonic ventral mesencephalic cells to DADLE (0.01 g/ml), prior to intrastriatal transplantation, enhanced functional recovery and graft survival in 6-hydroxydopamine-induced hemiparkinsonian rats. At 6 and 8 weeks posttransplantation, animals that received DADLE-treated cell grafts exhibited significantly higher (near normal) spontaneous locomotor behaviors, as well as trends of greater reversal of motor asymmetrical behaviors compared with animals that received nontreated cell grafts. Histological examination revealed that animals transplanted with DADLE-treated cell grafts exhibited about twice the number of surviving tyrosine hydroxylase-immunoreactive grafted neurons compared with those animals that received nontreated cell grafts. These results suggest that DADLE should be considered as an adjunctive agent for neural transplantation therapy in Parkinson's disease.
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PMID:Delta opioid peptide augments functional effects and intrastriatal graft survival of rat fetal ventral mesencephalic cells. 1129 72

D-Ala(2)-deltorphin I (DADTI) is a heptapeptide amide first extracted from frog skin that displays a high selectivity and affinity for delta opioid receptors. Previous studies using a polyclonal antiserum specific for its C-terminal tetrapeptide-amide (DVVG) have already described in rat and mouse brain the presence of immunoreactive neurons, most of them belonging to the mesencephalic dopaminergic neurons. C57BL/6J (C57) and DBA/2J (DBA) are two inbred strains of mice well known for showing marked genotype-dependent differences for phenotypes related to differential brain dopamine functioning. Brain specimens of both inbred mouse strains were frozen, cut and immunostained using the same antiserum. Some sections were also double immunostained with monoclonal anti-tyrosine hydroxylase (TH). DVVG-immunoreactive neurons were observed among both dopaminergic and non-dopaminergic neurons. DVVG- and TH-immunoreactive neurons were observed among the dopaminergic A8, A9 and A10 mesencephalic nuclei. They were on average 21.9% more numerous in DBA than in C57 mice. DVVG-immunoreactive nerve fibres could be seen in limbic, striatal, cortical and thalamic areas. The distribution patterns of DVVG-IR and TH-IR nerve fibres differed most conspicuously within the infralimbic, prelimbic and cingulate cortices, forming a dense network in DBA but rare in C57 mice. Non-dopaminergic DVVG-immunoreactive neurons did not differ significantly in the two strains. Our finding that the number and distribution pattern of this dopaminergic neuronal subpopulation differed in the two mouse strains could provide morphological support for the known behavioural differences between the DBA and C57 strains under normal and experimental conditions.
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PMID:Immunoreactive neurons in the brain of two mouse strains after incubation with an antiserum recognizing Asp-Val-Val-Gly.NH2 (DVVG), the C-terminal fragment of (D-Ala2)-deltorphin I. 1229 65