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)

An impairment of energy metabolism may underlie slow excitotoxic neuronal death in neurodegenerative diseases. We therefore examined the effects of intrastriatal, subacute systemic, or chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats. Following intrastriatal injection 3-NP produced dose-dependent striatal lesions. Neurochemical and histologic evaluation showed that markers of both spiny projection neurons (GABA, substance P, calbindin) and aspiny interneurons (somatostatin, neuropeptide Y, NADPH-diaphorase) were equally affected. Subacute systemic administration of 3-NP produced age-dependent bilateral striatal lesions with a similar neurochemical profile. However, in contrast to the intrastriatal injections, striatal dopaminergic afferent projections were spared. Both freeze-clamp measurements and chemical shift magnetic resonance spectroscopy showed that 3-NP impairs energy metabolism in the striatum in vivo. Microdialysis showed no increase in extracellular glutamate concentrations after systemic administration of 3-NP. The lesions produced by intrastriatal injection or systemic administration of 3-NP were blocked by prior decortication. However, the NMDA antagonist MK-801 did not block the effects of intrastriatal 3-NP, consistent with a non-NMDA excitotoxic mechanism. In contrast to subacute systemic administration of 3-NP, chronic (1 month) administration produced lesions confined to the striatum in which there was relative sparing of NADPH-diaphorase interneurons, consistent with an NMDA excitotoxic process. Chronic administration showed growth-related proliferative changes in dendrites of spiny neurons similar to changes in Huntington's disease (HD). These results are consistent with in vitro studies showing that mild metabolic compromise can selectively activate NMDA receptors while more severe compromise activates both NMDA and non-NMDA receptors. Chronic administration of 3-NP over 1 month produces selective striatal lesions that replicate many of the characteristic histologic and neurochemical features of HD.
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PMID:Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. 769 9

Substance P immunoreactivity is localized in discrete subsets of neurons in the human cerebral cortex and basal ganglia. In the normal human cerebral cortex, a subset of aspiny local circuit neurons in deep cortical layers and the cortical subplate contain preprotachykinin mRNA and substance P immunoreactive. These neurons, which contain NADPH diaphorase (NO synthase) activity, are strikingly depleted in Alzheimer's disease--in contrast to other local circuit neurons--suggesting that they may be an early target of the degenerative process. In the human basal ganglia, substance P immunoreactivity and mRNA are localized in a subset of spiny striatal neurons that project to the internal segment of the globus pallidus. These neurons are enriched in D1 dopamine receptors and dynorphin, and are calbindin and DARP 32 immunoreactive. A separate subset of aspiny striatal local circuit neurons also contain substance P immunoreactivity. Fiber and terminal staining is prominent in the matrix compartment of the ventromedial striatum and persists dorsally as a rim outlining patches that contain lesser amounts of immunoreactivity. Intense fiber and terminal staining is found in the pars reticulata of the substantia nigra. In Huntington's disease, substance P is depleted in the striatum in parallel with the dorsoventral gradient of neuronal loss. Terminal staining is progressively depleted in the pallidum and substantia nigra in tandem with striatal atrophy. Substance P receptor immunoreactivity, defined with two polyclonal antisera raised against synthetic peptides derived from the substance P receptor sequence, intensely labels a subset of large neurons in the nucleus basalis and striatum identical to neurons labeled with choline acetyltransferase and nerve growth factor receptor antibodies (although striatal cholinergic neurons do not contain nerve growth factor receptor immunoreactivity in the human). These cholinergic neurons resist degeneration in Huntington's disease but are sensitive to degeneration in Alzheimer's disease. Less intensely labeled neurons include pyramidal neurons in the hippocampal CA2 field, nonpyramidal neurons in CA1-4, pyramidal and nonpyramidal neurons in deep neocortical layers and in the cortical subplate. Substance P receptor immunoreactivity is not well defined in the human globus pallidus or substantia nigra.
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PMID:Substance P and substance P receptor histochemistry in human neurodegenerative diseases. 769 86

1. The role of endogenous nitric oxide (NO) as a modulator of enteric neurotransmission was investigated in longitudinal muscle myenteric plexus (LMMP) preparations of guinea-pig isolated ileum. 2. In tissues previously incubated with [3H]-choline, exogenous NO inhibited electrically-evoked [3H]-choline overflow as well as responses to exogenous agonists, indicating that NO has the potential of neuromodulation both pre- and postjunctionally. 3. A series of NO synthase inhibitors enhanced contractile responses to nerve stimulation indicating inhibitory neuromodulation by endogenous NO. 4. The potency order of the NO synthase inhibitors and their consistent effects after dexamethasone, on responses to nerve stimulation, indicate action on a constitutive NO synthase. 5. Responses enhanced by NO synthase inhibitors were inhibited by the substance P receptor antagonist, spantide, suggesting a neuromodulatory influence on substance P-like neurotransmission by the endogenous NO. 6. NO synthase inhibition did not modify contractile responses to application of acetylcholine or substance P, or [3H]-choline overflow, indicating that endogenous NO mainly has a prejunctional inhibitory action on substance P-like neurotransmission. Nor did it modify responses to direct electrical muscle stimulation in the presence of tetrodotoxin. This suggests a prejunctional enhancing effect by NO synthesis inhibition. 7. Evidence for endogenous NO modulation of acetylcholine release was obtained when NO synthase inhibition modified atropine-sensitive, nerve-mediated contractile responses. However, [3H]-choline overflow was unaltered by NO synthase inhibition. 8. NO synthase inhibition did not modify responses to inhibitory neurotransmission. 9. The findings suggest that endogenous NO inhibits substance P-like motor neurotransmission, probably via prejunctional mechanisms. Cholinergic transmission may also be reduced by endogenous NO, acting prejunctionally.
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PMID:Modulation of cholinergic and substance P-like neurotransmission by nitric oxide in the guinea-pig ileum. 769 59

Pancreatic ganglia are formed by neural crest-derived precursors, are innervated by enteric neurons, and contain neuropeptides. In addition, the enzyme NADPH-diaphorase is located in a subset of enteric and pancreatic neurons. The expression of neural markers (GAP-43 and NC-1), neurotransmitter-related markers (including neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), galanin (GAL), dopamine beta hydroxylase (DBH), substance P (SP), calcitonin gene-related peptide (CGRP)), and NADPH-diaphorase was studied in the fetal and neonatal rat gut and pancreas (E12-P28) in situ and in vitro. NC-1, GAP-43 and DBH-immunoreactive cells were found in the primordial stomach on day E12, and in the pancreas on day E13, along with NPY in endocrine cells. Pancreatic NPY-immunoreactive neurons were detected by day E18. CGRP was seen in the foregut at day E12 but not in the pancreas until day E14. Other neuropeptides (SP, GAL, GRP and VIP) all appeared in the foregut earlier than in the pancreas. NADPH-diaphorase activity was first found in situ in foregut neurons on day E13, and in the pancreas on day E14, but seen in explants a day earlier. These observations show that development of neurons occurs earlier in the gut than in the pancreas, and that NADPH-diaphorase activity appears earlier than the immunoreactivities of the neuropeptides.
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PMID:Appearance of neuropeptides and NADPH-diaphorase during development of the enteropancreatic innervation. 772 Feb 14

Colocalization of vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase, respectively, with NADPH-diaphorase staining in rat adrenal gland was investigated using the double labelling technique. All vasoactive intestinal peptide- and some neuropeptide Y-immunoreactive intrinsic neuronal cell bodies seen in the gland were double stained with NADPH-diaphorase. Double labelling also occurred in some nerve fibres immunoreactive to vasoactive intestinal peptide and neuropeptide Y in the medulla and cortex. No colocalization of calcitonin gene-related peptide, substance P or tyrosine hydroxylase immunoreactivity with NADPH-diaphorase staining was observed. However, nerve fibres with varicosities immunoreactive for all the neuropeptides examined were closely associated with some of the NADPH-diaphorase-stained neuronal cell bodies. Thus, in rat adrenal gland, nitric oxide is synthesized in all ganglion cells containing vasoactive intestinal peptide and in some containing neuropeptide Y, but not in those containing calcitonin gene-related peptide, substance P or tyrosine hydroxylase.
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PMID:Colocalization of neuropeptides and NADPH-diaphorase in the intra-adrenal neuronal cell bodies and fibres of the rat. 778 Oct 27

Histochemical staining was used to demonstrate that intramural neurons of the gallbladder contain NADPH-diaphorase, and therefore are likely to produce nitric oxide. A subset of the neurons in the gallbladders of the guinea pig, gerbil, opossum, dog, and human stained positively for the enzyme. In the guinea pig, all neurons that were immunoreactive for vasoactive intestinal peptide (VIP), also contained NADPH-diaphorase. Furthermore, neurons that were immunoreactive for neuropeptide Y, which have been shown to be immunoreactive for substance P and somatostatin as well, rarely contained NADPH-diaphorase. It is suggested that the VIP/NADPH-diaphorase-containing neurons represent intrinsic inhibitory motor neurons of the gallbladder, and that these neurons may have a role in the relaxation of the muscularis during gallbladder filling.
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PMID:NADPH-diaphorase and VIP are co-localized in neurons of gallbladder ganglia. 831 13

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

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24-9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24-9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24-9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24-9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24-9981-induced responses. Ro-24-9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24-9981 amplified this response in a specific receptor-mediated fashion.
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PMID:Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch. 856 41

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

Since it has been demonstrated recently that neuropeptides are involved in wound healing in vivo we investigated the role of substance P (SP), calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in regeneration of ultraviolet (UV) photodamaged rat skin by topical administration of specific antagonists. Topical application of the neurokinin (NK)1-receptor antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabi cyclo[ 2.2.2]octan-3-amine (CP-96,345) significantly delayed the reduction of the necrotic area at all timepoints post UV-irradiation, whereas topically administered NO synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in an increased necrotic area only at 7 days post-irradiation. More important, topically administered L-NAME but not SP reduced nuclear immunolabelling for proliferating cell nuclear antigen (PCNA) of the UV-exposed epidermis, suggesting a NO-mediated stimulation of keratinocyte proliferation. These findings suggest that endogenous SP and NO have a trophic function in wound healing after UV-induced damage of the skin which may be mediated by stimulation of angiogenesis or epidermal cell proliferation.
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PMID:Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. 858 55


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