Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.
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PMID:Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. 843 51

Previous studies have demonstrated that the epithelium of the respiratory portion of rat nasal mucosa is amply supplied by nerve fibers with immunoreactivities for calcitonin gene-related peptide (CGRP) and substance P (SP), these fibers most likely acting as sensory mediators in the mucosa. The present study demonstrates that some intraepithelial fibers contain a VIP-immunoreactivity whose occurrence in these nerves has previously been neglected. The present study further aims to confirm the occurrence of NO-producing intraepithelial nerve fibers in the rat nasal mucosa and to examine its colocalization with CGRP and with VIP. Double staining methods were used to evaluate the colocalization of NADPH-diaphorase. The reactivity for NADPH-diaphorase and that for CGRP coexisted in only a small part, if any, of the nerve fibers distributed at the basal portion of the epithelium. In the perpendicularly and obliquely oriented transepithelial nerve fibers, both reactivities were clearly demonstrated to be separated in different fibers. VIP immunoreactivity was also present in a part of the intraepithelial nerve fibers of the nasal mucosa, and their entire population was shown to be positive for NADPH-diaphorase. The NADPH-diaphorase-positive reaction was displayed in only a small population of neurons in the trigeminal ganglion, whereas it was seen in numerous neurons in sphenopalatine ganglion, being colocalized with VIP.
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PMID:Intraepithelial nerve fibers in the nasal mucosa of the rat with special reference to the localization of CGRP, VIP and nitric oxide (NO). 856 35

1. The effect of tachykinins on transepithelial potential difference (PD) of rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo were investigated. 2. Perfusion of tracheal mucosa with neurokinin A (NKA) or substance P (SP) dose dependently increased PD in the presence of amiloride, with the potency being NKA > SP, but neurokinin B (NKB) had no effect. 3. Application of NG-nitro-L-arginine methylester (L-NAME, 10(-3) M) attenuated the NKA-induced increase in the amiloride-sensitive PD, causing a rightward displacement of the dose-response curve by approximately 1.0 log U, whereas NG-nitro-D-arginine methylester (D-NAME, 10(-3) M) did not. 4. The inhibitory effect of L-NAME was reversed by L-arginine (10(-2) M) but not by D-arginine (10(-2) M). 5. The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. 6. NKA and SP increased [NO] in a dose-dependent manner, the maximal increase from the baseline value being 114 +/- 11 nM (mean +/- S.E.M., P < 0.001) and 54 +/- 6 nM (P < 0.01), respectively. 7. Histochemistry for NADPH diaphorase activity showed a strong staining within the epithelial cells. 8. We conclude firstly that tachykinins increase amiloride-sensitive PD in vivo, which probably reflects Cl- movement from the submucosa toward the respiratory lumen in tracheal mucosa, and secondly that NO generation by epithelial cells may be involved in this process.
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PMID:Role of nitric oxide in tachykinin-induced increase in potential difference of rabbit tracheal mucosa. 856 47

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
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PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

The antimitotic drug methylazoxymethanol was used to destroy striatal patch neurons during their three-day-period of neurogenesis in the rat. Single or multiple injections of methylazoxymethanol were given during embryonic days 13-15, the period when patch neurons are known to undergo their final cell division. Methylazoxymethanol treatments produced a dramatic reduction in striatal volume. Immunocytochemical analysis revealed the continued presence of patches of neurons that were substance P-immunoreactive and devoid of calbindin and enkephalin immunoreactivity. Both the number of patches and relative volume occupied by patches was reduced in methylazoxymethanol-treated striata. Patch neurons could also be labelled by an intrastriatal injection of FluoroGold during the first postnatal week. The early ingrowth of nigrostriatal dopamine afferents was less noticeably patchy in the methylazoxymethanol-treated animals, in part owing to an overall increase in density. Large reductions in the number of neurons immunoreactive for choline acetyltransferase were observed, whereas NADPH diaphorase-stained neurons were not reduced unless methylazoxymethanol was given on embryonic day 15. Injections of bromo-deoxy-uridine, either during or after the 24 h that each methylazoxymethanol injection was considered to be effective, revealed that (i) some patch neurons continued to be generated in the 24-h period following methylazoxymethanol administration, and (ii) many patch neurons were generated after the effects of methylazoxymethanol had worn off. These findings demonstrate that it was impossible to completely eliminate the patches using methylazoxymethanol injections during the period of patch neurogenesis. However, methylazoxymethanol treatment during this time did produce a dramatic loss of cells and a relatively greater reduction in patch volume. Despite this disruption, the appropriate compartmentalization of neuroactive substances appeared to be maintained.
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PMID:The development of striatal patch/matrix organization after prenatal methylazoxymethanol: a combined immunocytochemical and bromo-deoxy-uridine birthdating study. 857 71

Neurons in the human adrenal medulla, stained by the NADH-diaphorase reaction, were counted and their neurochemical markers were investigated by double labeling immunofluorescence with special reference to substance P. The findings indicate a significant participation of intramedullary nerve cell bodies in human adrenal innervation with 40.4 neurons/mm3 adrenal medulla. Substance P-immunoreactive neurons, which made up approximately 20% of all neurons, exhibited heterogeneity by co-localization of immunoreactivities for dynorphin, for cholecystokinin, and for neurofilament triplet. Substance-P-immunolabeled neurons were always nonreactive for calcitonin gene-related peptide, for vasoactive intestinal polypeptide, or for tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. These chemical phenotypes of intramedullary neurons reveal immunohistochemical similarities with postganglionic neurons in parasympathetic ganglia or with enteric neurons, suggesting a hitherto unrecognized functional significance of the intrinsic nervous system in the human adrenal gland.
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PMID:Immunohistochemical heterogeneity of nerve cells in the human adrenal gland with special reference to substance P. 860 96

The mediator accounting for the major relaxant responses to electrical field stimulation of human airways was previously identified as nitric oxide (NO). In the present study, we examined the distribution of the neuronal isoform of the NO-generating enzyme, nitric oxide synthase (bNOS, type I NOS) in nerve fibers of the human airways (trachea, large and small bronchi, bronchioli) as well as in human intrinsic and sensory ganglia of airway innervation by means of quantitative histochemistry (NADPH-diaphorase technique) and immunohistochemistry. Correlation with substance P (SP) and vasoactive intestinal peptide (VIP) was performed by double-labeling immunohistochemistry. NOS-containing nerve fibers were found to be present in the airway smooth muscle, around submucosal glands, around blood vessels and, very rarely, in the lamina propria. The innervation density of airway smooth muscle by NOS-containing nerve fibers decreased significantly from trachea to large-diameter bronchi to small-diameter bronchi, whereas NOS-containing nerve fibers were completely absent from bronchioli. Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers. In airway intrinsic ganglia, the number of NOS-containing neuronal cell bodies increased from 57% in the trachea up to 83% in small bronchi. Around these perikarya, many nerve fibers displaying VIP-immunoreactive (VIP-IR) or SP-IR were found. In the superior vagal sensory (i.e., jugular) ganglion most of the neuronal cell bodies contained either NOS-IR or SP-IR; a colocalization of both was not as frequent. These data contribute to the understanding of the morphologic basis underlying the functional differences of the neural relaxant responses mediated by NO at different levels of the airway tree.
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PMID:Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides. 868 Jun 82

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.
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PMID:Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis). 869 72

The presence and distribution of nitric oxide synthase (NOS)-immunoreactive nerve fibers associated with the guinea pig major cerebral arteries was studied by means of immunohistochemical, histochemical and ultrastructural techniques. Anterior arteries of the circle of Willis received a rich supply of perivascular nerve fibers containing NOS immunoreactivity while posteriorly localized arteries presented a moderate to sparse innervation. A double immunofluorescence staining technique revealed that NOS was localized in nerve fibers distinct from those displaying substance P or tyrosine hydroxylase. Combined immunofluorescence and histochemical staining of the same preparation indicated that NOS immunoreactivity was localized in putative cholinergic nerve fibers (identified by their acetylcholinesterase content) and that NADPH-diaphorase activity (a marker for NOS-containing neurons) was found in nerves which also possessed VIP immunoreactivity. The ultrastructural study revealed that NOS immunoreactivity was present in numerous nerve varicosities at the adventitial-medial border. These results suggest that NO and VIP co-exist in putative parasympathetic nerve fibers supplying the guinea pig cerebral arteries and may be release together in response to nervous stimulation.
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PMID:Nitroxidergic innervation of guinea pig cerebral arteries. 874 Jun 67

To measure the generation of nitric oxide (NO) by airway epithelial cells and to study the physiological role of NO in the regulation of epithelial functions, we studied ciliary motility of rabbit cultured tracheal epithelium in vitro and ion transport across tracheal mucosa in vivo. Isoproterenol dose-dependently increased ciliary beat frequency, as measured by photoelectric methods. Perfusion of tracheal mucosa with tachykinins increased the diffusion potential for chloride ions, as measured in the presence of amiloride under open-circuit conditions: the rank order of potency was neurokinin A > substance P >> neurokinin B. These responses to isoproterenol and to tachykinins were attenuated by pretreatment with NG-nitro-L-arginine methylester, and this attenuation was reversed by L-arginine. In contrast, NG-nitro-D-arginine methylester and D-arginine had no such effects. NO concentrations in the medium and perfusate were measured in realtime with an amperometric sensor specific to this molecule, and immersion of the electrode allowed detections of a polarographic current under unstimulated conditions. Addition of isoproterenol, neurokinin A, or substance P caused a rapid and dose-dependent increase in NO concentration. Histochemical examination for NADPH diaphorase activity in cultured epithelium showed strong staining within the cytoplasm. These results suggest that NO is spontaneously released from airway epithelial cells and that generation of this molecule may contribute to airway epithelial ciliary motility and chloride ion secretion mediated by beta-adrenoceptors and by tachyinin NK2 receptors.
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PMID:[Airway epithelium and nitric oxide]. 875 8


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