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)

We have examined the ability of a number of neuropeptides to increase tyrosine hydroxylase (TH) activity in the superior cervical ganglion in vitro. Secretin and vasoactive intestinal peptide (VIP) both increased TH activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, insulin, luteinizing hormone-releasing hormone, [D-Ala2, Met5]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin and VIP increased TH activity with an EC50 of 5 nM and 0.5 microM, respectively. The effects of these peptides were not altered by prior decentralization of the ganglia, by addition of hexamethonium (3 mM) and atropine (6 microM), or by lowering the concentration of calcium in the medium to 0.1 mM. Addition of carbachol (3 microM) potentiated the effects of both secretin and VIP on TH activity. Several gastrointestinal peptides with structural similarities to secretin and VIP were examined for their ability to increase TH activity. Glucagon, gastric inhibitory peptide and human pancreatic tumor growth hormone-releasing factor produced no effect at a concentration of 10 microM, while PHI increased enzyme activity.
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PMID:Acute stimulation of ganglionic tyrosine hydroxylase activity by secretin, VIP and PHI. 614 16

We studied the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat. Ganglia were preincubated with [32P]Pi and were then incubated in non-radioactive medium containing a variety of agents that are known to activate tyrosine hydroxylase in this tissue. Tyrosine hydroxylase was isolated from homogenates of the ganglia by immunoprecipitation followed by polyacrylamide gel electrophoresis. 32P-labelled tyrosine hydroxylase was visualized by radioautography, and the incorporation of 32P into the enzyme was quantitated by densitometry of the autoradiograms. Veratridine produced a concentration-dependent increase in the incorporation of 32P into tyrosine hydroxylase, with 50 microM veratridine producing a 5-fold increase in 32P incorporation. The nicotinic agonist, dimethylphenylpiperazinium (100 microM), caused a 7-fold increase in the phosphorylation of tyrosine hydroxylase. The effect of dimethylphenylpiperazinium was maximal within 1 min and decreased upon continued exposure of the ganglia to this agent. The actions of dimethylphenylpiperazinium and of veratridine were dependent on extracellular Ca2+. Muscarine, 8-Br-cAMP, forskolin, vasoactive intestinal peptide, isoproterenol, deoxycholate and phospholipase C also stimulated the incorporation of 32P into tyrosine hydroxylase. These data support the hypothesis that phosphorylation plays a role in activation of tyrosine hydroxylase produced by all of these agents.
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PMID:Phosphorylation of tyrosine hydroxylase in the superior cervical ganglion. 614 69

Incubation of rat superior cervical ganglia with dimethylphenylpiperazinium (30 microM) for 30 min resulted in a two-fold increase in tyrosine hydroxylase activity. This effect was completely inhibited by substance P (30 microM) but not by substance P-free acid, kassinin or physalaemin. Neither of these four peptides alone produced any change in the activity of tyrosine hydroxylase. The IC50 for the inhibitory effect of substance P was approximately 3 microM. Substance P did not inhibit the stimulatory effects of bethanechol or vasoactive intestinal peptide on this enzyme activity. Thus substance P, acting at a site which has a different pharmacology than previously characterized substance P receptors, selectively inhibits nicotinic stimulation of tyrosine hydroxylase activity. These data raise the possibility that substance P may modulate the nicotinic regulation of catecholamine synthesis in sympathetic ganglia in vivo.
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PMID:Substance P inhibits the acute stimulation of ganglionic tyrosine hydroxylase activity by a nicotinic agonist. 620 8

Nitric oxide synthase-like immunoreactivity was found in a subpopulation of sympathetic postganglionic neurons in the cat stellate and lower lumbar ganglia. In the ganglia of other segments such cells were rare. Double staining for tyrosine hydroxylase-like immunoreactivity and nitric oxide synthase-like immunoreactivity or the reduced nicotinamide adenine dinucleotide phosphate diaphorase reaction indicated that nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity was always co-localized and was confined to tyrosine hydroxylase-negative (presumably cholinergic) ganglion cells, and was present in most of them. The occurrence of nitric oxide synthase in two subpopulations of cholinergic postganglionic neurons was investigated in triple staining experiments. Presumptive sudomotor neurons have been previously defined as scattered cells containing calcitonin gene-related peptide-like immunoreactivity, usually accompanied by vasoactive intestinal peptide-like immunoreactivity: 99% of these contained nitric oxide synthase. Presumptive muscle vasodilator neurons have been previously identified as clumped cells with strong vasoactive intestinal peptide-like immunoreactivity but no calcitonin gene-related peptide-like immunoreactivity: 70% of these contained nitric oxide synthase. Sweat glands were found in the paw pad skin surrounded by varicose fibres showing calcitonin gene-related peptide-like immunoreactivity and vasoactive intestinal peptide-like immunoreactivity, confirming previous work. Such fibres also stained for nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity, although their staining was relatively weaker than in the corresponding cell bodies. Varicose fibres with the same chemical coding were also found around all large and most medium and small arteries in the paw skin as well as around arteriovenous anastomoses. Fibres with the muscle vasodilator coding (vasoactive intestinal peptide-like immunoreactivity without calcitonin gene-related peptide-like immunoreactivity) were not seen in paw skin. These results suggest that nitric oxide may act as a co-transmitter (with acetylcholine, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide) in sudomotor neurons and (with acetylcholine and vasoactive intestinal peptide) in vasodilator neurons. Collateral branches of sudomotor neurons may innervate skin vessels, and release vasodilator transmitters including nitric oxide to cause the vasodilatation which provides the fluid supply for sweat formation. Alternatively, separate vasodilator neurons to skin may share the same chemical code as sudomotor neurons.
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PMID:Nitric oxide synthase and chemical coding in cat sympathetic postganglionic neurons. 747 30

Using immunohistochemical techniques a small population of choline acetyltransferase (ChAT) immunoreactive (IR) neurones has been identified in the inferior mesenteric ganglion (IMG) of guinea pig (4.6% of all neurones), ferret (6.4%) and rat (0.4%). A detailed study in the guinea-pig IMG revealed that the vast majority of cholinergic neurones did not express tyrosine hydroxylase (TH)-IR, indicating that they were non-catecholaminergic. The cholinergic neurones were significantly larger than the TH-positive neurones. The majority of the ChAT-IR cells (64%) was observed in small clusters which were consistently located in the caudal lobe of the IMG close to the entry of the hypogastric nerves. 83% of the ChAT-IR cells also contained neuropeptide Y (NPY). Since the vast majority of TH-negative cells were ChAT-positive (94%), the TH negativity was taken as an indirect indication for ChAT-IR. NPY-IR, somatostatin (SOM)-IR and vasoactive intestinal peptide (VIP)-IR were found in both the TH-IR cells (22, 84 and 1%, respectively) and the putative cholinergic population (95, 84 and 70, respectively). Thus the majority of cholinergic neurones in the IMG were likely to contain NPY, SOM and VIP. TH-IR cells exhibited an extensive innervation of fibers immunoreactive for ChAT, VIP, ENK and NOS. In contrast, only a sparse plexus of ChAT-, ENK-, NOS-, NPY- and SOM-positive fibres was found around the TH-negative cells. VIP-IR fibres did not appear to innervate ChAT neurones.
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PMID:Choline acetyltransferase-immunoreactive neurones in a prevertebral sympathetic ganglion, the inferior mesenteric ganglion. 749 Apr 21

The distribution of neuropeptide- (neuropeptide Y, substance P, vasoactive intestinal peptide) and catecholamine-synthesizing enzyme-immunoreactive axons in guinea-pig trigeminal, nodose, and cervical dorsal root ganglia was studied by double-labelling immunofluorescence in controls and after extirpation of either the cervical sympathetic trunk or the stellate ganglion; tyrosine hydroxylase- and dopamine-beta-hydroxylase-immunoreactive terminals in dorsal root ganglia were ultrastructurally investigated. Six neurochemically identifiable axons innervated the trigeminal ganglion, five kinds were found in the nodose and dorsal root ganglia. Two of them (catecholaminergic with and without neuropeptide Y) were of sympathetic origin and, besides their termination at arteries, provided a direct innervation of capsule cells of the trigeminal and cervical dorsal root ganglia facing the subarachnoid space. Varicosities which were interpreted as being of sensory origin were equally numerous in all ganglia, whereas those being likely of parasympathetic origin decreased in numbers from the trigeminal to the dorsal root and nodose ganglia. It is concluded that the sensory ganglia are the target of postganglionic sympathetic, parasympathetic and primary afferent neurons, each of which are specifically organized with respect to the neurochemical phenotype and inter- and intraganglionic distribution. Among other targets, these "nervi gangliorum" appear to be intimately linked to the ganglionic capsular cells and meningeal sheaths facing the liquor spaces.
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PMID:Sensory ganglia as a target of autonomic and sensory nerve fibres in the guinea-pig. 751 9

The distribution and patterns of colocalization of nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were examined in nerve fibers supplying the human lower ureter using double label immunofluorescence. Many nerve fibers immunoreactive for NOS were observed within the ureter. Positive varicose fibers were seen running longitudinally within the smooth muscle bundles, particularly those of the inner layers of the ureter. Immunoreactive axons were also prominent within the subepithelium, and as plexi surrounding many blood vessels. The colocalization studies indicated that NOS was never present in presumptive sympathetic nerve fibers expressing TH. All fibers containing VIP, however, were also immunoreactive for NOS. In addition, a minor population of NOS fibers did not contain VIP. Neuropeptide Y coexisted with NOS in a significant number of nerve terminals, although fibers expressing only NPY were equally common. Several immunochemically distinct nerve populations can therefore be distinguished in the human ureter: (1) nerves containing NOS either with or without VIP; (2) NOS-immunoreactive fibers with NPY; and (3) those fibers expressing TH or NPY which do not contain NOS. The results indicate that some non-noradrenergic peptide-containing nerves in the human ureter have the capacity to synthesize nitric oxide (NO), and that NO may be involved in the regulation of ureteric motility.
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PMID:Colocalization of nitric oxide synthase with vasoactive intestinal peptide, neuropeptide Y, and tyrosine hydroxylase in nerves supplying the human ureter. 752 Sep 52

In an immunohistochemical study, we find that galanin is much more widely distributed in the peripheral innervation of the cat eye than in other animals so far examined. Previous studies of rat and pig eyes have revealed sparse galanin-positive nerves that presumably originate in the trigeminal ganglion. In contrast, the cat has a rich supply of galanin-containing nerve fibers throughout the uvea. Galanin-positive varicose nerves concentrate densely in iris muscles and distribute more sparsely in the ciliary muscle. The ciliary processes have a plexus of galanin-positive nerves underlying the ciliary epithelium at their base and positive nerve fibers coursing within their stroma. The ciliary artery and its branch vessels in the uvea are invested with a dense plexus of galanin-positive nerves. All autonomic ganglia supplying the eye contain cells that express galanin. It is present in 97% of superior cervical ganglion cells, coexisting with both tyrosine hydroxylase and neuropeptide Y; in 80% of pterygopalatine ganglion cells, most of which also contain vasoactive intestinal peptide; and in approximately 25% of ciliary ganglion cells. After unilateral superior cervical ganglionectomy, galanin-positive nerves almost totally disappear from the iris muscles, demonstrating that they are predominantly of sympathetic origin. Galanin-positive nerves investing the ciliary artery and choroidal blood vessels are not detectably reduced by sympathectomy, indicating that perivascular parasympathetic nerves from the pterygopalatine ganglion also express galanin. Other galanin-containing nerves in the eye can originate from the trigeminal and ciliary ganglia. The prominence of galanin in the ocular autonomic innervation of the cat provides an opportunity to explore the physiological effects of this neuropeptide in the eye.
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PMID:Galanin immunoreactivity in autonomic innervation of the cat eye. 752 68

The aim of this study was to investigate the neurochemical coding of myenteric neurons in the guinea pig gastric corpus by using immunohistochemical methods. Antibodies and antisera against calbindin (CALB), calretinin (CALRET), choline acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP), dopamine beta-hydroxylase (DBH), beta-endorphin (ENK), neuropeptide Y (NPY), neuron-specific enolase (NSE), nitric oxide synthase (NOS), protein gene product 9.5 (PGP), parvalbumin (PARV), serotonin (5-HT), somatostatin (SOM), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. Double- and triple-labeling studies revealed colocalization of certain transmitters and enabled the identification of distinct subpopulations of gastric enteric neurons. NPY/VIP/NOS/ENK were present in 28% of all neurons, whereas 11% had NPY/VIP/DBH/ChAT; NOS-only neurons made up 2% of the population. The combination SP/ChAT/ENK occurred in 21% of the population, whereas SP/ChAT/ENK/CALRET and SP/CHAT/SOM/ +/- CALRET was identified in 5% and 6% of all cells, respectively. 5-HT-containing neurons comprised 2% of all cells and could be further classified by the presence of additional antigens as 5-HT/SP/(ChAT) or 5-HT/VIP/(ChAT). Approximately 21% of all neurons contained only ChAT with no additional antigen present and are referred to as ChAT/-. Gastric myenteric ganglion cells were not immunoreactive for CALB, PARV, CGRP, or TH. The results of this study indicate that gastric myenteric neurons can be characterized on the basis of different chemical coding. Neurochemical coding of corpus myenteric neurons revealed some similarities and significant differences in comparison with other regions of the gut. These differences might reflect adaptation of enteric nerves according to regional specialization and the distinct functions of the proximal stomach as a gastric reservoir.
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PMID:Neurochemical coding of enteric neurons in the guinea pig stomach. 753 52

The peptidergic innervation of the human superficial temporal artery was investigated by means of immunohistochemical, ultrastructural, and in vitro pharmacological techniques. A dense network of nerve fibers was found in the adventitia. The majority of the nerve fibers displayed immunoreactivity for tyrosine hydroxylase and neuropeptide Y (NPY). A moderate supply of perivascular nerve fibers displayed either acetylcholinesterase activity or immunoreactivity for vasoactive intestinal peptide (VIP), peptide histidine methionine-27 (PHM), and calcitonin gene-related peptide (CGRP). Only a few nerve fibers displayed substance P (SP), neurokinin A (NKA), and neuropeptide K (NPK) immunoreactivity. In double immunostained preparations, SP immunoreactivity was co-localized with NPK and CGRP in the same nerve fibers. Ultrastructural studies revealed the presence of numerous axon variocosities at the adventitial--medial border. NPY, VIP, and CGRP immunoreactivities occurred in the same type of large granular vesicles, but in morphological distinct nerve profiles. NPY had, in general, no direct vasoconstrictor effect. However, at a low concentration of NPY contractile response induced by NA (10(-7)-10(-6)M) was 9-15 times enhanced. The NPY-induced potentiation of the NA-induced contraction was not dependent on the presence of an intact endothelium. No significant difference was found between acetylcholine, VIP, and PHM in either potency or degree of relaxation. SP, NKA, and CGRP also acted as vasodilatory agents, with CGRP being more potent than the tachykinins. The response to SP, but not CGRP, was dependent on an intact endothelium. Pretreatment of the vessels with a low concentration of NPY did not change the responses to ACh, VIP, SP, or CGRP.
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PMID:The peptidergic innervation of the human superficial temporal artery: immunohistochemistry, ultrastructure, and vasomotility. 754 Feb 93


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