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)

SK&F 29661 (1,2,3,4-tetrahydro-7-isoquinoline-sulfonamide) is a potent and selective in vitro and in vivo inhibitor of adrenal phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28). Its Ki value for in vitro inhibition of rat adrenal PNMT was 133 nM. In vivo, the adrenal conversion of 3H-norepinephrine to 3H-epinephrine was maximally inhibited by a single oral dose of 100 mg/kg. In long term chronic studies in rats, adrenal epinephrine was reduced by SK&F 29661 in a dose dependent fashion to greater than 90%, without substantial increases in norepinephrine. Urinary excretion of epinephrine was significantly reduced by the drug both basally and following 2-deoxy-D-glucose stimulation. No drug related changes were found in plasma corticosterone values and only small effects were observed on adrenal tyrosine hydroxylase and PNMT enzyme levels. The cardiac norepinephrine pool and its turnover time were both significantly reduced; its turnover rate, however, was only slightly increased. Our studies indicate that SK&F 29661 is a highly effective, non-toxic and novel pharmacological tool which is useful in depleting adrenal epinephrine stores via inhibition of its biosynthesis.
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PMID:Studies on the long term effects of SK&F 29661 upon adrenal catecholamines. 612 96

Newborn rats were daily injected with 0.2 mg hydrocortisone acetate for seven days. They were killed 1, 7 or 21 days after the last injection, together with untreated controls. Hydrocortisone caused a great increase in the number of the small, intensely fluorescent (SIF) cells and the appearance of similar small cells with intense immunohistochemical reactions for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine (noradrenaline) N-methyltransferase (PNMT) in the superior cervical ganglion. At the same time, the adrenaline content and the PNMT activity of the ganglion greatly increased, while no significant changes were observed in the dopamine or noradrenaline content or TH or DBH activity. All these changes essentially disappeared after a recovery period of seven or 21 days. It is concluded that hydrocortisone caused a temporary increase in the number of SIF cells by causing a synthesis of TH, DBH and PNMT in previously existing small, non-fluorescent cells, which start to synthesize and store adrenaline, thus becoming intensely fluorescent SIF cells. These SIF cells are different from the normal SIF cells of the same ganglion, most of which appear at a later stage of postnatal development when response to hydrocortisone is lost, which contain TH but neither DBH nor PNMT, and which permanently remain in the ganglion.
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PMID:Effect of hydrocortisone on catecholamines and the enzymes synthesizing them in the developing sympathetic ganglion. 612 66

Intraventricular injection of colchicine in rat results in the appearance within hypothalamus of numerous neurons containing the adrenaline-synthesizing enzyme, phenylethanolamine N-methyltransferase, but not the other catecholamine biosynthetic enzymes. Increased PNMT staining in hypothalamus was paralleled by an increase in PNMT activity measured in micropunch preparations. Immunotitration demonstrated that this increase was due to accumulation of specific enzyme protein. The finding that hypothalamic neurons express PNMT without tyrosine hydroxylase suggests that such neurons may produce methylated amines other than adrenaline.
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PMID:A new group of neurons in hypothalamus containing phenylethanolamine N-methyltransferase (PNMT) but not tyrosine hydroxylase. 614 73

The changes of phenylethanolamine-N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme that catalyzes the final step in the biosynthesis of adrenaline, were studied during the development of several regions of rat brain. PNMT is present in medulla oblongata-pons, hypothalamus, cerebellum, and midbrain five days before birth, and a progressive increase in the enzyme activity is observed during development. The adult levels are attained between 15 and 20 days, depending on the region. The increases in PNMT activity in the rostral regions are higher than in the caudal regions. PNMT attains adult levels earlier than tyrosine hydroxylase and dopamine-beta-hydroxylase. The apparatus for adrenaline synthesis seems to be mature at three weeks after birth in the medulla oblongata-pons, which contains the cell bodies of adrenaline-containing neurons. In the other regions the adult levels of enzyme activity are attained at 15 days after birth.
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PMID:Regional changes in phenylethanolamine-N-methyltransferase of rat brain during development. 743 37

In the rostral ventrolateral medulla (RVLM), angiotensin II (Ang II) receptors are concentrated in the region that contains neurons innervating sympathetic preganglionic neurons. We sought to determine whether these bulbospinal cells are sensitive to Ang II. Retrogradely labeled bulbospinal RVLM neurons (N = 125) were recorded in thin slices from neonatal rats. Most (33 of 46) histologically recovered bulbospinal neurons were C1 cells (immunoreactive for tyrosine hydroxylase [TH-ir] or phenylethanolamine N-methyltransferase [PNMT-ir]). Bulbospinal RVLM neurons were spontaneously active (2.7 +/- 0.2 spikes per second, n = 69) with 'resting' potential of -54 +/- 0.4 mV (n = 77) and input resistance of 879 +/- 53 M omega (n = 47). Ang II (0.3 to 1 mumol/L) increased the spontaneous firing rate of most bulbospinal neurons (+250%, 28 of 39). In current-clamp mode, Ang II (1 mumol/L) produced depolarization (+6.8 +/- 0.6 mV, n = 59 neurons) and increased input resistance (+21 +/- 2%, n = 36 neurons). In voltage-clamp mode, Ang II elicited an inward current (9.7 +/- 0.9 pA; holding potential, -40 to -55 mV; n = 25 neurons) that reversed polarity at the K+ equilibrium potential (n = 8 neurons) and was barium sensitive (n = 4 neurons). Ang II-evoked conductance change was voltage independent (-40 to -140 mV, n = 8 neurons). The effects of Ang II were blocked by losartan (9 of 9 neurons) but persisted in low Ca2+/high Mg2+ (7 of 7 neurons). Ang II-sensitive cells were inhibited by alpha 2-adrenergic receptor agonists (12 of 15 neurons). Ang II excited 91% (30 of 33) of TH-ir or PNMT-ir cells but 23% (3 of 13) of non-TH-ir neurons. In conclusion, RVLM bulbospinal cells express Ang II type-1 receptors whose activation leads to a reduction in resting K+ conductance.
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PMID:Angiotensin II decreases a resting K+ conductance in rat bulbospinal neurons of the C1 area. 857 71

Neural stimulation of the cornea induces conjunctival goblet cell mucous secretion. Immunofluorescence microscopy was used to determine if nerves are present near conjunctival goblet cells and what types of nerves are present. In euthanized rats, the local anesthetic lidocaine (1%) was placed topically on the ocular surface for 10 min to prevent goblet cell mucous secretion. The ocular surface tissues were removed and either fixed in formaldehyde and then frozen, or frozen first and then post-fixed in formaldehyde. Tissue was sectioned and nerves localized by indirect immunofluorescence microscopy, using antibodies to synaptophysin (indicates nerve, independent of type), vasoactive intestinal peptide (VIP, indicates parasympathetic nerves), tyrosine hydroxylase (TH, indicates sympathetic nerves), dopamine beta-hydroxylase (DBH, indicates sympathetic nerves), phenylethanolamine-N-methyltransferase (PNMT, indicates sympathetic nerves), and calcitonin gene-related peptide (CGRP, indicates sensory nerves). Goblet cells were identified by phase-contrast microscopy. Synpatophysin-containing nerves were present in the basolateral region of conjunctival goblet cells clusters. Nerve fibers immunoreactive to VIP were found in the conjunctiva along the epithelial-stromal junction and around the basolateral aspect of goblet cell clusters. Nerve fibers immunoreactive to TH and DBH were detected surrounding goblet cells and in the conjunctival stroma. Nerve fibers immunoreactive to CGRP were detected in the epithelium and at the epithelial stromal junction, but were not localized near goblet cell clusters. CGRP-containing nerve fibers were also detected in the conjunctival stroma under the epithelium. We conclude that efferent parasympathetic and sympathetic, but not afferent sensory, nerves appear to be located adjacent to conjunctival goblet cell clusters. Activation of efferent parasympathetic and sympathetic nerves could directly stimulate conjunctival goblet cell mucous secretion. Antidromic activation of afferent sensory nerves releasing neurotransmitters could stimulate goblet cell secretion by a paracrine mechanism.
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PMID:Localization of nerves adjacent to goblet cells in rat conjunctiva. 858 38

Postnatal development of the innervation of the porcine pineal gland by tyrosine hydroxylase-(TH-), dopamine-beta-hydroxylase-(D beta H), phenylethanolamine-N-methyltransferase-(PNMT-) and neuropeptide Y- (NPY-) immunoreactive (IR) nerve fibres was examined using the double-labelling immunohistochemical technique. TH-IR nerve fibres appeared in the pineal gland of new-born piglets and formed plexus in the capsula and connective tissue septa of the gland. In 20-day-old pigs and older ones, the nerve terminals branched off from the plexus and penetrated into adjacent parenchyma. The nerve fibres formed network; its density increased with age and depended on the region of the gland. In mature pigs, some differences in the innervation pattern between cortex and medulla were also observed. Most of TH-IR fibres were also D beta H- and NPY-positive. Some PNMT-positive fibres were noted in new-born piglets, but not in older animals. NPY-IR fibres were distributed in pattern overlapping that observed in the case of TH- and D beta H-IR fibres. Most of NPY-IR fibres were also positive for TH.
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PMID:Postnatal changes in adrenergic and neuropeptide Y-containing nerve fibres in pineal gland of the pig. An immunohistochemical study. 885 Oct 52

TrkA high-affinity receptors are essential for the normal development of sympathetic paravertebral neurons and subpopulations of sensory neurons. Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which aspects of development of the adrenal medulla might be regulated via TrkA are unknown. In the present study we demonstrate that mice deficient for TrkA, but not the neurotrophin receptor TrkB, show an early postnatal progressive reduction of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in preganglionic sympathetic neurons within the thoracic spinal cord, which are also significantly reduced in number. Quantitative determinations of specific AChE activity revealed a massive decrease (-62%) in the adrenal gland and a lesser, but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers of the adrenal medulla and its innervation, including various neuropeptides, chromogranin B, secretogranin II, amine transporters, the catecholamine-synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1, essentially were unchanged. Interestingly, AChE immunoreactivity appeared unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal medullary cells, do not express TrkA. They must, therefore, be affected indirectly by the TrkA knock-out, possibly via a retrograde signal from chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves.
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PMID:Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. 899 44

1. The development of tyrosine hydroxylase-immunoreactive (TH-IR) neurons was examined in the spinal cord of the chick embryo and hatchling. 2. Two groups of TH-IR cells are described, both of which appear to reach their full complement in number relatively late in embryonic development. One group is comprised of numerous cells located ventral to the central canal which make direct contact with the lumen of the canal. The other group consists of large multipolar neurons that reside in the dorsal horn, more commonly along the outer margin of the gray matter within lamina I and II, and less frequently deeper in the dorsal horn within medial portions of laminae V, VI or VII. 3. TH-IR cells ventral to the central canal in the chick are comparable in location to dopamine (DA)-containing spinal cord cells in lower vertebrate species. In contrast, the dorsally-suited TH-IR cells in the chick are known only to occur in similar positions in higher vertebrates. Therefore, the chick is novel in that the presence of both groups of TH-IR cells appearing together in significant numbers within the spinal cord has not been shown in any other species studied to date. 4. The TH-containing cells in the chick cord do not appear to contain the catecholamine biosynthesis enzymes, DBH or PNMT. Moreover, using anti-DA immunocytochemistry, neither group of TH-IR cells demonstrated detectable levels of DA in control animals nor in animals pretreated with inhibitors of MAO (MAO-I). 5. However, a difference was noted though between the two TH-IR cell groups in terms of their responses to exogenously supplied L-DOPA, the immediate precursor to DA. With the administration of L-DOPA and a MAO-I to chick hatchlings, cells in the region ventral to the central canal stained intensely for DA. In contrast, the same treatment failed to produce DA-immunoreactive cells in the dorsal horn. 6. One reasonable hypothesis for these results is that the TH-IR cells ventral to the central canal contain an active form of AADC, the enzyme that converts L-DOPA to DA. With this interpretation, if these cells can produce DA from L-DOPA, yet do not appear to synthesize DA endogenously, it would appear that the TH enzyme contained in these cells occurs in an inactive form. Whether the TH enzyme in the dorsally located immunoreactive cells is also inactive is uncertain since it remains unclear whether they contain AADC.
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PMID:Tyrosine hydroxylase-containing neurons in the spinal cord of the chicken. I. Development and analysis of catecholamine synthesis capabilities. 901 27

The rostral ventrolateral medulla (RVLM) contains barosensitive, bulbospinal neurons that provide the main supraspinal excitatory input to sympathetic vasomotor preganglionic neurons. However, the phenotype of the critical RVLM cells has not been conclusively determined. The goal of the current study was to identify the proportion of electrophysiologically defined, putative, presympathetic RVLM neurons that are C1 cells. We used a juxtacellular labeling technique to individually fill spontaneously active, barosensitive, bulbospinal RVLM neurons with biotinamide following electrophysiological characterization in chloralose-anesthetized rats. To determine whether these neurons could be classified as C1 cells, the biotinamide-labeled cells were processed for detection of tyrosine hydroxylase. The majority of barosensitive bulbospinal RVLM neurons were tyrosine hydroxylase immunoreactive (TH-ir; 28 of 39). All of the barosensitive bulbospinal RVLM neurons with axonal conduction velocities in the C fiber range (<1 m/second) were TH-ir (n = 16), whereas faster conducting cells (1 to 7 m/second) were either lightly TH-ir (n = 12) or not detectably TH-ir (n = 11). Adjacent respiratory-related RVLM units labeled with biotinamide were not detectably TH-ir (n = 10). To verify that TH-ir cells were indeed adrenergic, a subset of barosensitive bulbospinal cells labeled with biotinamide were examined for phenylethanolamine N-methyltransferase immunoreactivity (PNMT-ir). Three slowly conducting cells had detectable PNMT-ir, and two fast-conducting cells had no detectable PNMT-ir. These results indicate that the majority of bulbospinal RVLM neurons with putative sympathoexcitatory function are C1 cells.
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PMID:Identification of C1 presympathetic neurons in rat rostral ventrolateral medulla by juxtacellular labeling in vivo. 937 11


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