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)

Recently, we have shown increases in the immunoreactivity for neuropeptide Y and tyrosine hydroxylase in the insular cortex surrounding the focal infarction after middle cerebral artery occlusion. In addition, the immunoreactivity for neuropeptide Y, leucine-enkephalin, dynorphin, and neurotensin increased ipsilaterally in the amygdala. Increases in immunoreactivity were observed in nerve terminals and fibers; changes in the neuropeptides were maximal 3 days after stroke. Local excitotoxic injury of the insular cortex also elicited similar neuropeptide changes unilaterally in the same regions. In this study, immunohistochemistry was used following intracerebroventricular injection of colchicine and stroke to determine whether blockade of axonal transport would prevent these neurochemical changes. These experiments would also locate the putative cellular origins of the neurochemicals involved. Control rats received either colchicine injection or middle cerebral artery occlusion alone. Injection of colchicine enhanced the periinfarct increase in neuropeptide Y but did not alter the increase in tyrosine hydroxylase. The neuropeptide Y increase was observed in local cortical neurons. Colchicine prevented the increases in immunoreactivity for the neuropeptides in the amygdala on the side of stroke, although there were small perikarya that showed immunoreactivity for these neuropeptides within the amygdala on both sides. We conclude that local cortical neurons are responsible for the increase in neuropeptide Y in the periinfarct region, that the cortical increase in tyrosine hydroxylase is not dependent on fast axonal transport, and that axonal transport of signals from the insular cortex to the amygdala is critical in mediating the amygdalar neuropeptide changes seen after stroke.
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PMID:Colchicine affects cortical and amygdalar neurochemical changes differentially after middle cerebral artery occlusion in rats. 933 Nov 69

This study has used multiple-labelling immunohistochemistry and quantitative analysis to examine the projections of subpopulations of parasympathetic and sympathetic neurons to different vascular and secretory structures in five cranial exocrine glands of guinea-pigs. Multiple subpopulations of parasympathetic axons, identified by immunoreactivity (IR) for various combinations of peptides, innervated arteries, arterioles, ducts and acini in sublingual, submandibular, parotid, lacrimal and zygomatic glands, although axons were absent from ducts in the parotid gland. Most parasympathetic axons contained IR for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), with or without enkephalin (Enk). The proportion of parasympathetic axons that contained Enk-IR varied greatly between target tissues and glands: Enk-IR was more common in axons supplying secretory ducts, acini and arterioles than in axons innervating more proximal arteries; Enk-IR was less common in axons supplying the lacrimal gland than axons supplying the submandibular, lacrimal and zygomatic glands. Sympathetic axons with IR for tyrosine hydroxylase (TH) innervated arterial vessels in all glands, but innervated secretory structures only in the salivary glands. Sympathetic axons supplying proximal arterial segments often contained NPY-IR and sometimes also contained IR for dynorphin. Dynorphin-IR was more common in axons in the parotid, lacrimal and zygomatic glands than in the sublingual and submandibular glands. In contrast, axons supplying arterioles, ducts and acini lacked peptide IR. These results indicate that neuronal pathways regulating proximal arteries in cranial exocrine glands are different from the neuronal pathways regulating arterioles and acini, and may be different from neurons projecting to proximal secretory ducts. Furthermore, the peptides enkephalin, NPY and dynorphin are likely to make variable contributions to autonomic neurotransmission in different arterial segments and in different cranial exocrine glands.
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PMID:Selective innervation of different target tissues in guinea-pig cranial exocrine glands by sub-populations of parasympathetic and sympathetic neurons. 933 96

Neuronal circuitry between the inferior mesenteric ganglion (IMG) and the distal colon as well as the rectum, forming the intestino-intestinal reflex pathway, was investigated in the dog using immunohistochemistry combined with retrograde tract tracing and denervation experiments. Virtually all IMG neurons were tyrosine hydroxylase (TH)-immunoreactive. Of these ganglionic neurons, about 64% were also immunoreactive for calbindin (Calb), some 35% for neuropeptide Y (NPY), and 2% for vasoactive intestinal peptide (VIP). The retrograde tracer experiments revealed that both Calb/TH neurons and NPY/TH neurons projected to the distal colon and the rectum. In these intestinal walls, Calb/TH positive varicose fibers were found in the myenteric and submucous ganglia as well as in the longitudinal muscle layer, while NPY/TH positive fibers were mainly distributed around the vascular walls. Around Calb/TH neurons of the IMG, abundant varicose nerve fibers immunoreactive for VIP, dynorphin (DYN), calcitonin gene-related peptide (CGRP), enkephalin (ENK), substance P (SP) and bombesin (BOM) were distributed. These immunoreactive fibers disappeared after the total denervation of the IMG. After the application of Fast Blue into the IMG or distal stumps of transected lumbar colonic and hypogastric nerves, retrogradely labeled neurons occurred in the myenteric plexus with increasing density along the distal colon and rectum, and were immunoreactive for VIP, DYN, CGRP, ENK, SP or BOM. Double immunostaining of nerve fibers in the distal stumps of the ligated colonic and hypogastric nerves revealed the presence of viscerofugal fibers containing VIP with DYN and/or CGRP and those containing ENK with SP and/or BOM. These results demonstrate for the first time that the efferent limb of the canine intestino-intestinal reflex arch via the IMG consists of Calb-immunoreactive ganglion neurons projecting to the longitudinal muscles in addition to the enteric plexus of the lower intestine and also of NPY-immunoreactive ganglion neurons projecting to the intestinal blood vessels, and that the afferent limb is composed of at least two discrete groups with different peptide contents, i.e., myenteric neurons containing VIP with DYN and/or CGRP and those containing ENK with SP and/or BOM.
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PMID:Neuronal circuitry between the inferior mesenteric ganglion and lower intestine of the dog. 941 42

Enzyme histochemistry and immunohistochemistry were used to determine the types of nerves supplying the ampullary gland, coagulating gland, dorsolateral prostate, ventral prostate and seminal vesicle of the male golden hamster. Quantitative change of dopamine beta-hydroxylase (DbetaH), and neuropeptide Y (NPY) immunoreactive and acetylcholinesterase-stained (AChE-stained) nerves with age was also determined. Using an antibody against protein gene product 9.5, nerves were seen to distribute in subepithelial connective tissues, smooth muscles and adventitial connective tissues. Presumptive catecholaminergic nerves immunoreactive for DbetaH and tyrosine hydroxylase were found mainly in periacinar smooth muscles, while AChE-stained nerves predominantly ramified subepithelial connective tissues. In addition, nerves immunoreactive to NPY, calcitonin gene-related peptide, leu-enkephalin, galanin, substance P, and vasoactive intestinal peptide were also detected. Quantitative estimation at 10, 52 and 78 weeks of age showed that densities of DbetaH and NPY nerves were halved by 52 weeks of age. This level was maintained in older animals. The density of AChE-stained nerves in all glands did not change with age. The ampullary gland appeared to have more AChE-stained nerves. These results were discussed from a comparative viewpoint and with regard to possible implications of aging of peripheral nerves on functioning of the male accessory sex glands.
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PMID:Innervation of accessory sex glands in the adult male golden hamster and quantitative changes of nerve densities with age. 943 Apr 39

Orphanin FQ (OFQ) is a novel heptadecapeptide whose structure resembles that of dynorphin A1-17. Its receptor shares appreciable homology with mu-, delta- and kappa-opioid receptors, and is highly expressed in the hypothalamus. The present study examined the effects of OFQ on neurons within the arcuate nucleus (ARC) of the mediobasal hypothalamus, using intracellular recordings from coronal slices. In current clamp, OFQ produced a hyperpolarization of ARC neurons, including those immunopositive for beta-endorphin, tyrosine hydroxylase and gonadotropin-releasing hormone. This hyperpolarization was dose-dependent, insensitive to antagonism by naloxone and was associated with a decrease in input resistance. In voltage clamp, OFQ produced an outward current associated with an increase in conductance. Varying the extracellular K+ concentration shifted the reversal potential for the OFQ response to the degree predicted by the Nernst equation. Furthermore, barium chloride markedly attenuated both the OFQ-induced hyperpolarization and decrease in input resistance. Administration of maximally effective concentrations of OFQ, followed by coadministration of maximal concentrations of either OFQ and the mu-opioid receptor agonist DAMGO or OFQ and the GABAB receptor agonist baclofen produced additive hyperpolarizations and outward currents. If DAMGO was applied first, followed by the coadministration of DAMGO and OFQ, then the responses were occluded. Taken together, these results indicate that OFQ inhibits beta-endorphin neurons, as well as A12 dopamine and GnRH neurosecretory cells, within the ARC by activating a subset of inwardly-rectifying K+ channels. This suggests that OFQ is not only an antiopioid peptide, but that it also modulates the hypothalamo-pituitary axis and, ultimately, reproductive behavior.
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PMID:The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance. 950 37

The innervation of the knee joint synovial membrane of the guinea pig, i.e., the synoviocyte layer, the subjacent connective tissue and the connective tissue region beneath, was analyzed with immunohistofluorescence and electron microscopy. A screening of the innervation with antibodies against the general axon marker -- protein gene product (PGP) 9,5 -- revealed the presence of nerve fibers distributed in various regions of the knee joint synovial membrane. Confirming previous studies, some of these nerve fibers stained with antibodies to tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). In addition, dynorphin (DYN)-containing fibers were detected, which have not been reported previously in normal joints. In general, the immunoreactive fibers were observed close to the synoviocytes and at blood vessels. Fibers with colocalization of NPY- and TH-like immunoreactivities (LIs), as well as of DYN- and TH-LIs were demonstrated. In the electron microscope, bundles of unmyelinated fibers as well as single fibers were found in the connective tissue region below the synoviocytes. Varicose parts of the nerve fibers contained mainly small, clear vesicles. Small and large dense-cored vesicles were also seen, but less frequently. Denser portions of the plasma membranes of some axons were observed in these regions, facing the extracellular space. Myelinated fibers were also observed in some nerve bundles. These findings emphasize the complex innervation of the synovial membrane, with nerve fibers containing a host of neuroactive substances. Altogether, these fibers are probably involved in many functions such as vasoregulation and control of synovial secretion in addition to being a source of mediators in joint inflammation.
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PMID:The innervation of the synovium of the knee joint in the guinea pig: an immunohistochemical and ultrastructural study. 956 22

To ascertain cocaine's effects in the fetus, we developed a nonhuman primate model in which pregnant monkeys were administered cocaine (3 mg/kg i.m.) or saline four times a day from day 20 through days 40-70 of a 165-day gestation. At the time of cesarean section, plasma levels of cocaine in fetal blood were 231 +/- 70 ng/ml. Fetal brains were examined using immunocytochemistry, in situ hybridization, receptor autoradiography, and nuclease protection assay analysis. No differences were found in the expression of tyrosine hydroxylase and dopamine receptor mRNAs by days 40-45 of gestation. However, by day 60 the midbrain of monkeys exposed to cocaine had significantly reduced expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Moreover, dopamine D1 and D2 receptor mRNAs were significantly elevated in the rostral forebrain as were D1 and D2 receptor binding sites in days 60-70 cocaine-exposed fetuses. Cocaine treatment from day 20 to days 60 and 70 of gestation also significantly increased the mRNA concentrations of dynorphin and enkephalin in the rostral forebrain. These findings suggest that in utero cocaine exposure has profound effects on the developing dopamine neurocircuitry.
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PMID:Changes in the midbrain-rostral forebrain dopamine circuitry in the cocaine-exposed primate fetal brain. 966 6

The aim of the present study was to analyze the neurochemical properties of the centrifugal visual system (CVS) of the quail using an immunohistochemical approach by testing 16 neuropeptides (angiotensin: ANG, bradykinin: BK, cholecystokinin, dynorphin, L and M-enkephalin, beta-endorphin: beta-END, galanin, alpha-neoendorphin, neurokinin A, neuropeptide Y (NPY), ocytocin, somatostatin, substance P, vasopressin, vasoactive intestinal polypeptide) and three neurotransmitters or their synthetic enzymes (choline acetyltransferase: ChAT, tyrosine hydroxylase: TH, serotonin: 5-HT and nitric oxide synthase: NOS, including the histochemical nicotinamide adenine dinucleotide phosphate diaphorase technique). For each substance, the somatic and afferent fiber and terminal labeling was analyzed within the nucleus isthmo-opticus (NIO) and the ectopic area (EA) and compared with that of retinopetal cell bodies labeled retrogradely with RITC following its intraocular injection (double-labeling procedure). The results showed that none of the centrifugal neurons were reactive to any of the substances tested. In contrast, all with the exception of ANG, BK and beta-END, labeled fibers and terminals within the EA and only four (ChAT, 5-HT, NPY and NOS) within the NIO. Possible sources of these immunoreactive fibers terminating in the NIO and EA were investigated by mapping the somatic immunolabeling of the different substances within brainstem regions previously shown by Miceli and other authors to project upon the centrifugal neurons. The data suggests that, besides the rapid retino-tecto-NIO-retinal loop, which facilitates the transfer of meaningful or more relevant information within particular portions of the visual field, the multiple afferent input which stems from various brainstem regions utilizes a wide range of neuroactive substances. Some of these afferent projections upon the centrifugal neurons appear to belong to nonspecific systems which might play a role in modulating the excitability of centrifugal neurons as a function of arousal.
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PMID:An immunohistochemical study of putative neuromodulators and transmitters in the centrifugal visual system of the quail (Coturnix japonica). 971 61

Abnormalities of the enteric nervous system are thought to explain the pathophysiology of motility disorders. Our aim was to determine if particular classes of enteric neurons are affected in slow transit constipation (STC). Specimens were taken from the terminal ileum and ascending, transverse and descending colon of patients undergoing subtotal colectomy for STC. Immunohistochemistry was performed using antisera to neuron-specific enolase, tachykinin, leu-enkephalin, choline acetyltransferase, vasoactive intestinal peptide, nitric oxide synthase, tyrosine hydroxylase and neuropeptide Y. The density of nerve fibres labelled with these antibodies in each layer was compared with age-matched controls. The density of nerve fibres with tachykinin and enkephalin immunoreactivity was reduced in the colonic circular muscle of the 15 patients with STC, whereas innervation of all other layers was normal. This reduction of tachykinin-immunoreactive nerve fibres also occurred in nine of the 12 specimens of terminal ileum examined. No difference was detected in the density or distribution of nerve fibres using the other antisera. Excitatory nerve fibres are present in the circular muscle in STC but they are deficient in tachykinins and enkephalin.
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PMID:Abnormalities of nerve fibers in the circular muscle of patients with slow transit constipation. 987 Jan 63

The neurochemical profile was examined at postnatal day 3-4 in mutant mice generated by in vivo Cre mediated activation of an attenuated diphtheria toxin gene inserted into the D1 dopamine receptor gene locus. An earlier study of this model had shown that D1 dopamine receptor, substance P and dynorphin were not expressed in the striatum. Quantitative in situ hybridization analysis showed an increase in D2 dopamine receptor and enkephalin messenger RNA expression. The nigrostriatal pathway in the mutant pups was intact with a normal number of dopaminergic neurons in the substantia nigra and the ventral tegmental area in addition to a normal pattern of striatal dopamine transporter and tyrosine hydroxylase immunoreactivity. Quantitative analysis of striatal dopamine transporter density using [3H]mazindol showed a reduction of 26% suggesting a degree of transneuronal down-regulation. There was also a 49% reduction of striatal GABA receptor binding and a 36% reduction of striatal muscarinic receptor binding in mutant pups. The number of healthy striatal neuropeptide Y-containing interneurons was also substantially down-regulated in the mutant striatum. In contrast, there was an increase in the number of striatal cholinergic interneurons. Down-regulated cortical GABA receptor and muscarinic receptor binding was also observed in addition to subtle morphological changes in the neuropeptide Y-expressing population of cortical neurons. The changes reflect the early cascade of events which follows the ablation of D1 dopamine receptor-positive cells. Although extensive changes in a number of striatal and cortical neurons were demonstrated, only subtle transneuronal effects were seen in the nigrostriatal pathway.
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PMID:Early direct and transneuronal effects in mice with targeted expression of a toxin gene to D1 dopamine receptor neurons. 1068 9


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