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)

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

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.
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PMID:The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers. 167 20

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.
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PMID:Molecular anatomy of the neuro-immune connection. 177 30

Neuropeptide-Y (NPY) is a 36 amino acid peptide that acts as a chemical messenger in the central and peripheral nervous systems. NPY often is found colocalized with the classical neurotransmitter norepinephrine (NE) and can potentiate the effects of this neurotransmitter postsynaptically in many systems. Using immunocytochemistry for NPY and specific lymphoid cell markers, we mapped the distribution of NPY-positive nerve fibers in the rat spleen. NPY-positive nerve fibers were present along the vasculature, trabeculae, and capsule, and also were found associated with specific lymphoid parenchymal compartments of the spleen, in close contact with lymphocytes and macrophages. These contacts were investigated further at the electron microscopic level. NPY-positive nerve terminals were found in close apposition with lymphocytes in the periarteriolar lymphatic sheath, and with lymphocytes and macrophages in the marginal zone. Previous studies have reported that postganglionic noradrenergic nerve fibers innervate specific lymphoid compartments of the rat spleen, with nerve terminals forming direct appositions with cells of the immune system. The possible colocalization of NPY and NE in these nerve fibers was investigated by chemical sympathectomy with 6-hydroxydopamine, followed by immunocytochemical labeling of NPY and tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis. Colocalization also was investigated by labeling for NPY with a fluorescent label, eluting the NPY, and staining for TH with diaminobenzidine as the label. These studies demonstrate that norepinephrine and NPY are colocalized in the postganglionic sympathetic nerve fibers of the rat spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. 190 53

The presence of tyrosine hydroxylase (TH) and vasoactive intestinal polypeptide (VIP) in the nerve fibers of the human palatine tonsil and paratonsillar secretory glands is reported. By immunohistochemistry TH-immunoreactive nerves and those immunoreactive to VIP were localized to the tonsil, in particular, the tonsillar vessel wall, extranodular lymphoid tissue and lymph nodule, and to the acinar basal surface of the paratonsillar glands. In the lymph nodule, immunoreactive varicose nerve profiles were observed inside the marginal zone. The germinal center was devoid of immunoreactive fibers.
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PMID:Immunolocalization of tyrosine hydroxylase and vasoactive intestinal polypeptide in nerve fibers innervating human palatine tonsil and paratonsillar glands. 197 67

Previous work has established that the central nervous system can modulate the immune response. Direct routes through which this regulation may occur are the sympathetic and sensory innervation of lymphoid organs. We investigated the innervation of canine mesenteric lymph nodes using immunohistochemistry and the expression of binding sites for sensory neuropeptides using quantitative receptor autoradiography. The sympathetic innervation of lymph nodes was examined by immunohistochemical methods using an antiserum directed against tyrosine hydroxylase (TOH), the rate limiting enzyme in catecholamine synthesis. TOH-containing fibers were associated with 90% of the blood vessels (arteries, veins, arterioles and venules) in the hilus, medullary and internodular regions of lymph nodes and in trabeculae with no obvious relationship to blood vessels. The sensory innervation of lymph nodes was investigated using antisera directed against the putative sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP- and SP-containing fibers were detected in the hilus, the medullary region, and the internodular region of lymph nodes usually in association with arterioles and venules. About 50% of the arterioles and venules exhibited a CGRP innervation and a smaller fraction (5-10%) were innervated by SP-containing fibers. Few if any TOH, CGRP, and SP nerve fibers were detected in the germinal centers of lymph nodes. Using quantitative receptor autoradiography we studied the distribution of receptor binding sites for the sensory neuropeptides CGRP, SP, substance K (SK), vasoactive intestinal peptide (VIP), somatostatin (SOM), and bombesin. Specific CGRP binding sites were expressed throughout lymph nodes by trabeculae, arterioles, venules and 25% of the germinal centers. SP receptor binding sites were localized to arterioles and venules in the T cell regions and 25-30% of the germinal centers. VIP binding sites were localized to the internodular and T cell regions, to medullary cords, and to 10-20% of germinal centers. SK, SOM, and bombesin binding sites were not detected in the lymph nodes, although receptor binding sites for these peptides were detected with high specific/nonspecific binding ratios in other canine peripheral tissues. Taken together with previous results these findings suggest that the sympathetic and sensory innervation of mesenteric lymph nodes appears to be involved with the regulation of their blood and lymph flow. The neuropeptide receptor binding sites in lymph node germinal centers may be expressed by lymphocytes upon activation by antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes. 245 53

By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in the white pulp of the spleen at birth, among surface IgM-positive (sIgM+) B lymphocytes at the outer border of the periarteriolar lymphatic sheath (PALS), distant from the central artery. During the first 7 days, noradrenergic innervation developed rapidly, forming plexuses of nerve fibers along the central artery and its branches, among T and B lymphocytes of the PALS, and along the developing marginal sinus where ED3+ macrophages accumulate. The splenic concentration of NE (per mg wet wt.) and 3-methoxy-4-hydroxy-phenetheleneglycol (MHPG), a NE metabolite, increased rapidly during this period, suggesting that NE is available and released from these nerves. From 7-14 days, the white pulp expanded to include an inner PALS, outer PALS, marginal sinus, and marginal zone; during this period, TH+ fibers arborized principally among T lymphocytes of the inner PALS and adjacent to macrophages along the marginal sinus. By 14 days of age, NE concentration reached adult levels, although the MHPG/NE ratio (an index of NE turnover) remained higher throughout development than in adulthood. Finally, from 14-28 days, the outer PALS expanded to include follicles containing sIgM+ B lymphocytes. At the earliest stages of follicular development, a parafollicular rim of noradrenergic fibers was present, providing occasional branches which arborized within the follicle. No further changes were observed in either noradrenergic innervation or cellular compartmentation after 28 days of age. These findings suggest that noradrenergic fibers are present in developing compartments of the spleen at the earliest stages of their development, providing norepinephrine for interaction with a variety of adrenoceptor-bearing lymphoid and nonlymphoid cells.
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PMID:Parallel development of noradrenergic innervation and cellular compartmentation in the rat spleen. 292 Jul 90

Sympathetic noradrenergic nerve fibers, stained with antiserum for tyrosine hydroxylase (TH), richly innervate the splenic white pulp. These fibers distribute with the vascular and trabecular systems, and associate mainly with the central artery and its branches, the periarteriolar lymphatic sheath (PALS), the marginal sinus, and the parafollicular zone, with occasional delicate fibers also present in the follicles. Simultaneous staining of TH-positive nerve fibers and markers for specific lymphoid cells has shown several regions of contact between nerves and lymphocytes or macrophages. The TH-positive nerve fibers in the plexuses around the central arterial system and in the PALS are present among T lymphocytes (OX-19-positive cells) including both T helper and T suppressor cells, and interdigitating cells. At the marginal sinus, TH-positive fibers run adjacent to macrophages (ED3-positive cells), B lymphocytes (IgM-positive), and intensely fluorescent IgM-positive cells. Along the parafollicular zone, TH-positive nerve fibers run adjacent to T lymphocytes, peripheral follicular B lymphocytes, and intensely fluorescent IgM-positive cells. Within some follicles, delicate fibers end adjacent to both T and B lymphocytes. These relationships suggest a direct interaction between norepinephrine release from the TH-positive nerve terminals and the lymphocytes and macrophages closely associated with them, and focuses attention on the potential neural modulation of related functions such as T and B lymphocyte entry into the spleen and antigen capture (marginal zone), antigen presentation and T cell activation (PALS), B cell activation (parafollicular zone and marginal zone), and lymphocyte egress (outer marginal zone).
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PMID:Noradrenergic sympathetic innervation of the spleen: I. Nerve fibers associate with lymphocytes and macrophages in specific compartments of the splenic white pulp. 331 80

Intracellular recordings were made from smooth muscle cells of arterioles and the capsule of the spleen of guinea-pig and rat, and the responses to periarterial or subcapsular nerve stimulation were recorded. The innervation of the spleen was studied using fluorescence and immunohistochemical techniques. Catecholamine-containing axons were associated with smooth muscle of the splenic capsule, trabeculae, arterioles and amongst cells of the periarteriolar lymphoid sheath. Axons immunoreactive for neuropeptide Y (NPY) and tyrosine hydroxylase were distributed in an identical manner to catecholamine-containing axons, whereas axons immunoreactive for substance P or calcitonin gene-related peptide were present at a very low density in spleens from both species. In segments of arterioles, single transmural stimuli evoked excitatory junction potentials (EJPs) of 1-10 mV amplitude. EJPs facilitated during short trains of stimuli (1-10 Hz) and summated at 10 Hz, often initiating a muscle action potential. EJPs persisted in the presence of prazosin (1 microM) and idazoxan (1 microM), but were abolished by the P2x-purinoceptor antagonist suramin (1 mM). Spontaneous depolarizations were observed in smooth muscle cells of arterioles and capsule. Some events in arterioles were observed in the presence of suramin and so may originate postjunctionally independently of transmitter release. As single transmural stimuli failed to evoke a depolarization in capsular smooth muscle, spontaneous depolarizations in this tissue probably also arise postjunctionally. Short trains of high frequency stimuli (10-35 Hz) evoked biphasic depolarizations of capsular smooth muscle cells. The initial component peaked 2.5 s following the onset of stimulation; the second component peaked 15 s following the onset and decayed exponentially with a time constant of 15 s. By fitting a product of exponentials to the second component, it was possible to define the initial component, which decayed with a time constant of around 1.5 s. Neurally evoked depolarizations of capsular smooth muscle were abolished by 1 microM TTX. Blockade of alpha 1-adrenoceptors with prazosin reduced the initial component of the depolarization, whereas alpha 2-adrenoceptor blockade with idazoxan virtually abolished the second component. In some cells a small, faster depolarization persisted after alpha-adrenoceptor blockade. The slow alpha 2-adrenoceptor-mediated depolarization was identical to that recorded in the rat tail artery and in the guinea-pig mesenteric vein. The data indicate that sympathetic neuroeffector transmission from noradrenergic axons containing NPY to splenic arterial and capsular smooth muscle occur by different mechanisms.
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PMID:Electrophysiological events during neuroeffector transmission in the spleen of guinea-pigs and rats. 791 66

The presence of peptidergic and noradrenergic sympathetic nerve fibers in specific compartments of both primary and secondary lymphoid organs of the rodent is well established. These nerve fibers directly contact lymphocytes and macrophages, as well as vascular and trabecular smooth muscle. We investigated the noradrenergic and neuropeptide-Y innervation of lymphoid organs in the cetacean, Delphinapterus leucas (beluga whale). The spleen, thymus, tonsil, gut-associated lymphoid tissue, and assorted lymph nodes were collected from five belugas, obtained during sanctioned hunts, and processed for catecholamine fluorescence histochemistry and for tyrosine hydroxylase and neuropeptide-Y immunocytochemistry. Innervation studies revealed fluorescent nerve fibers, tyrosine hydroxylase, and neuropeptide-Y positive nerve fibers in parenchymal lymphoid compartments, where they were closely associated with cells of the immune system, and in vascular and trabecular compartments. In lymphoid zones, tyrosine hydroxylase and neuropeptide-Y positive nerve fibers were observed in the periarteriolar lymphatic sheath and marginal zone of the spleen; in the outermost portion of the cortex, the corticomedullary zone, and medulla of the lymph nodes; in the parafollicular zones, and diffuse lymphocyte layer below the epithelium of the tonsil; in the outermost portion of some thymic lobules; and in the lamina propria of the gut. These findings are similar to those described for other mammals and substantiate an anatomical link between the nervous and immune systems in the beluga, whereby central nervous system activity may influence autonomic outflow to lymphoid organs and effect immunologic reactivity.
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PMID:Noradrenergic and peptidergic innervation of lymphoid organs in the beluga, Delphinapterus leucas: an anatomical link between the nervous and immune systems. 793 71


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