UNIPROT:P20366 - FACTA Search

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)

The present case, 78-years-old female, had been troubled with SMON during 28 years, and was suddenly died from cerebral hemorrhage. The neuropathology characteristic for SMON could not be revealed in the spinal cord on routine histological preparations. There were decreasing number of immunopositive granules in the nucleus gracilis of medulla oblongata for synaptophysin, and in the marginal zone of the lumbar dorsal horn for substance P. These findings showed the presence of tractus gracilis degeneration and the disappearance of nociceptive fibers from the dorsal roots, respectively. To elucidate the histopathological changes of the spinal cord in long standing cases with SMON, the 11 cases reported were reviewed. The mean duration from the onset to death was 22.8 years(16 to 33 years). The mean age was 76.3 years old(54 to 92), and the 10 cases were female. All cases showed sensory impairment of the lower extremities, while deep tendon reflex exaggerated was seen in 7 cases. There were nine cases involving dorsal funiculi degeneration of the spinal cord, in contrast the lateral funiculi alternation were noticed in only two cases. It was considered that the corticospinal tract alteration becomes undiscernible during the long course, although the dorsal funiculi degeneration remained.
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PMID:[Neuropathology of longstanding subacute myelo-optico-neuropathy (SMON): an autopsy case of SMON with duration of 28 years]. 1159 84

The P2X(7) purinergic receptor subtype has been cloned and emphasized as a prototypic P2Z receptor involved in neurotransmission in the central nervous system and ATP-mediated lysis of macrophages in the immune system. Less is known about the neurobiology of P2X(7) receptors in the enteric nervous system (ENS). We studied the distribution of the receptor with indirect immunofluorescence and used selective agonists and antagonists to analyze pharmacologic aspects of its electrophysiologic behavior as determined with intracellular "sharp" microelectrodes and patch-clamp recording methods in neurons identified morphologically by biocytin injection in the ENS. Application of ATP or 2'- (or-3'-) O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzBzATP) activated an inward current in myenteric neurons. Brilliant blue G, a selective P2X(7) antagonist, suppressed the responses to both agonists. Potency of the antagonist was greatest (smaller IC(50)) for the current evoked by BzBzATP. The P2X(7) antagonists 1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-piperazine (KN-62) and oxidized ATP also suppressed the BzBzATP-activated current. Micropressure application of BzBzATP evoked rapidly activating depolarizing responses in intracellular studies with "sharp" microelectrodes. Oxidized-ATP suppressed these responses in both myenteric and submucosal neurons. Rapidly activating depolarizing responses evoked by application of nicotinic, serotonergic 5-HT(3), or gamma-aminobutyric acid A (GABA(A)) receptor agonists were unaffected by brilliant blue G. Immunoreactivity for the P2X(7) receptor was widely distributed surrounding ganglion cell bodies and associated with nerve fibers in both myenteric and submucous plexuses. P2X(7) immunoreactivity was colocalized with synapsin and synaptophysin and surrounded ganglion cells that contained either calbindin, calretinin, neuropeptide Y, substance P, or nitric oxide synthase. The mucosa, submucosal blood vessels, and the circular muscle coat also showed P2X(7) receptor immunoreactivity.
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PMID:P2X(7) receptors in the enteric nervous system of guinea-pig small intestine. 1174 25

10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 +/- 5% of control by DA (100 microM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 microM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 microM), depressed EPSCs to 73 +/- 4% of control. The D2-like receptor antagonist, sulpiride (20 microM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 +/- 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 +/- 2.2 to 6.2 +/- 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.
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PMID:Dopamine modulates synaptic transmission in the nucleus of the solitary tract. 1242 8

We examined immunohistochemically whether the vesicular glutamate transporters (VGluTs), VGluT1 and VGluT2, might be expressed in synaptic terminals of nociceptive primary afferent fibers within laminae I and II of the medullary and spinal dorsal horns of the rat. VGluT1 immunoreactivity (IR) was intense in the inner part of lamina II but weak in lamina I and the outer part of lamina II. VGluT2-IR was most intense in lamina I and the outer part of lamina II. Expression of VGluTs in synaptic terminals was confirmed by dual immunofluorescence histochemistry for VGluTs and synaptophysin. Expression of VGluTs in axon terminals of primary afferent fibers terminating in laminae I and II was also confirmed immunohistochemically after unilateral dorsal rhizotomy. The dual immunofluorescence histochemistry indicated expression of VGluTs in substance P (SP)-containing axon terminals in lamina I and the outer part of lamina II. Electron microscopy confirmed the coexpression of VGluTs and SP in axon terminals within laminae I and II; VGluTs was associated with round synaptic vesicles at the asymmetric synapses. It was further observed that isolectin IB4, a marker for unmyelinated axons, often bound with VGluT2-immunopositive structures but rarely with VGluT1-immunopositive structures in lamina II. Thus, the results indicated in laminae I and II of the medullary and spinal dorsal horns that both VGluT1 and VGluT2 were expressed in axon terminals of primary afferent fibers, including SP-containing nociceptive fibers and that VGluT in unmyelinated primary afferent fibers terminating in lamina II was primarily VGluT2.
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PMID:Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat. 1254 8

Neurons in rat superficial dorsal horn that express neurokinin receptor 1 (NK1), a receptor for substance P, play a critical role in the development of hyperalgesia. Thermal hyperalgesia is dramatically reduced after ablation of these neurons, but, paradoxically, not in mice that lack the NK1 receptor (Mantyh et al. [1997] Science 278:275-279). Because primary afferents that express vanilloid receptor 1 (VR1), a receptor for noxious heat, are essential for thermal nociception and hyperalgesia, we reasoned that VR1-positive fibers may terminate onto NK1-expressing dorsal horn neurons. We therefore combined immunofluorescent staining for VR1 and NK1 to show that NK1-positive neurons in lamina I are contacted by VR1-positive fibers. That these contacts represent synapses was verified by staining for the presynaptic marker synaptophysin and by electron microscopy. By combining retrograde tracing with immunocytochemistry, we also found that most NK1-positive cells contacted by VR1-positive fibers project to the lateral parabrachial nucleus. Because quantitative evaluation suggests a preferential targeting of NK1-positive lamina I neurons by fibers containing VR1, these results demonstrate a significant monosynaptic innervation of spinoparabrachial neurons by VR1-positive afferents.
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PMID:VR1-positive primary afferents contact NK1-positive spinoparabrachial neurons. 1268 89

We used multiple-labeling immunohistochemistry and confocal microscopy to examine co-expression of immunoreactivity for vesicular glutamate transporters (VGluTs), synaptic vesicle proteins, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in peptide-containing sensory neurons of guinea pigs, mice, and toads. Axon terminals in the superficial layers of the dorsal horn of the spinal cord with immunoreactivity (IR) for both substance P (SP) and calcitonin gene-related peptide (CGRP) lacked IR for synaptosome-associated protein of 25 kDa (SNAP-25), syntaxin, synaptotagmin, synaptophysin, and synapsin, although adjacent varicosities without neuropeptides had IR for these synaptic proteins. Similarly, peptide-containing axon terminals in the superficial dorsal horn lacked IR for VGluT1 and VGluT2, despite the presence of VGluT2-IR in nearby nonpeptide varicosities. VGluT3-IR was sparse in the dorsal horn of the mouse spinal cord and was not present in peptide-containing axons. Most peripheral terminals of sensory neurons with both SP-IR and CGRP-IR in the skin, viscera, and autonomic ganglia of guinea pigs and mice also lacked IR for synaptic vesicle proteins, SNARE proteins, VGluT1, and VGluT2. In dorsal root ganglia from guinea pigs and mice, most small neurons with IR for both SP and CGRP lacked IR for SNAP-25, VGluT1, and VGluT2. Thus, proteins considered essential for vesicular uptake and exocytotic release of glutamate are not expressed at detectable levels by most sensory neurons containing SP and CGRP in rodents and toads. These data raise the possibility that most peptide-containing sensory neurons may not normally release glutamate as a transmitter.
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PMID:Most peptide-containing sensory neurons lack proteins for exocytotic release and vesicular transport of glutamate. 1567 99

Mesenchymal stem cells (MSCs) exhibit immune-suppressive properties, follow a pattern of multilineage differentiation, and exhibit transdifferentiation potential. Ease in expansion from adult bone marrow, as well as its separation from ethical issues, makes MSCs appealing for clinical application. MSCs treated with retinoic acid resulted in synaptic transmission, based on immunostaining of synaptophysin and electrophysiological studies. In situ hybridization indicated that the neurotransmitter gene preprotachykinin-I was expressed in these cells. However, translation of this gene only occurred after stimulation with interleukin (IL)-1 alpha. This effect was blunted by costimulation with IL-1 receptor antagonist. This study reports on the ability of MSCs to be transdifferentiated into neurons with functional synapses with the potential to become polarized towards producing specific neurotransmitters.
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PMID:Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha. 1574 33

Natriuretic peptides (NP) and the corresponding receptors are present in the rodent spinal cord. We have studied the structures which respond to atrial natriuretic peptide, brain natriuretic peptide, or C-type natriuretic peptide with an increased synthesis of cGMP. NP-responsive cGMP-producing structures were observed in laminae I-III, and X, and in addition in ependymal cells, astrocytes and a subpopulation of dorsal root ganglion cells. As the cGMP concentration is controlled by the rate of synthesis and the rate of breakdown by phosphodiesterases, we studied NP-responsive structures in spinal cord slices incubated in the presence of different phosphodiesterase inhibitors. We studied EHNA and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitors, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. Double immunostainings showed that cGMP-IR colocalized partial with the vesicular acetylcholine transporter molecule in lamina X, with Substance P in a subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation of CGRP-IR dorsal root ganglion neurons. Colocalization of cGMP-IR was absent with parvalbumin, synaptophysin, and the vesicular transporter molecules for GABA and glutamate. It is concluded that NPs in the spinal cord are probably involved in integrating intersegmental sensory processing in the spinal cord although the greater part of the NP-responsive cGMP-producing fibers could not be characterized. PDE2, 5, and 9 are involved in regulating NP-stimulated cGMP levels in the spinal cord. NPs may have a role in regulating cerebrospinal fluid homeostasis.
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PMID:ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord. 1662 44

NO-responsive, cGMP-producing structures are abundantly present in the cervical spinal cord. NO-mediated cGMP synthesis has been implicated in nociceptive signaling and it has been demonstrated that cGMP has a role establishing synaptic connections in the spinal cord during development. As cGMP levels are controlled by the activity of soluble guanylyl cyclase (synthesis) and the phosphodiesterase (PDE) activity (breakdown), we studied the influence of PDE activity on NO-stimulated cGMP levels in the rat cervical spinal cord. cGMP-immunoreactivity (cGMP-IR) was localized in sections prepared from slices incubated in vitro. A number of reported PDE isoform-selective PDE inhibitors was studied in combination with diethylamineNONOate (DEANO) as a NO-donor including isobutyl-methylxanthine (IBMX) as a non-selective PDE inhibitor. We studied 8-methoxy-IBMX as a selective PDE1 inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5 inhibitor, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. cGMP-IR structures (nerve fibers, axons, and terminals) were characterized using the following neurochemical markers: vesicular transporter molecules for acetylcholine, GABA, and glutamate (type 1 and type 2), parvalbumin, glutamate transporter molecule EAAT3, synaptophysin, substance P, calcitonin gene-related peptide, and isolectin B4. Most intense cGMP-IR was observed in the dorsal lamina. Ventral motor neurons were devoid of cGMP-IR. cGMP-IR was observed in GABAergic, and glutamatergic terminals in all gray matter laminae. cGMP-IR was abundantly colocalized with anti-vesicular glutamate transporter 2 (vGLUT2), however not with the anti-vesicular glutamate transporter 1 (vGLUT1), suggesting a functional difference between structures expressing vGLUT1 or vGLUT2. cGMP-IR did not colocalize with substance P- or calcitonin-gene related peptide-IR structures, however did partially colocalize with isolectin B4 in the dorsal horn. cGMP-IR in cholinergic structures was observed in dorsal root fibers entering the spinal cord, occasionally in laminae 1-3, in laminae 8 and 9 in isolated boutons and in the C-type terminals, and in small cells and varicosities in lamina 10. This latter observation suggests that the proprioceptive interneurons arising in lamina 10 are also NO-responsive. No region-specific nor a constant co-expression of cGMP-IR with various neuronal markers was observed after incubation of the slices with one of the selected PDE inhibitors. Expression of the mRNA of PDE2, 5, and 9 was observed in all lamina. The ventral motor neurons and the ependymal cells lining the central canal expressed all three PDE isoforms. Incubation of the slices in the presence of IBMX, DEANO in combination with BAY 41-2272, a NO-independent activator of soluble guanylyl cyclase, provided evidence for endogenous NO synthesis in the slice preparations and enhanced cGMP-IR in all lamina. Under these conditions cGMP-IR colocalized with substance P in a subpopulation of substance P-IR fibers. It is concluded that NO functions as a retrograde neurotransmitter in the spinal cord but that also postsynaptic structures are NO-responsive by producing cGMP. cGMP-IR in a subpopulation of isolectin B4 positive fibers and boutons is indicative for a role of NO-cGMP signaling in nociceptive processing. cGMP levels in the spinal cord are controlled by the concerted action of a number of PDE isoforms, which can be present in the same cell.
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PMID:The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO-dependent and NO-independent cGMP production in the rat cervical spinal cord. 1662 45

Transient receptor potential channels (TRPC) are plasma membrane, non-selective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx. The expression, at mRNA level, of several TRPCs has been demonstrated recently in dopaminergic neurons of the substantia nigra (SN). The aim of the present study was to characterize the expression of TRPC1, at a protein level, in the substantia nigra neurons and non-excitable cells of Wistar rats. Single-label immunohistochemistry and double-label immunofluorescence were used to study the expression of TRPC1 among substantia nigra dopamine neurons and cellular processes using antibodies against tyrosine hydroxylase (TH), substance P (SP), enkephalin, synaptophysin, vesicular glutamate transporter-2 (Vglut-2), microtubule associated protein-2 and metabotropic glutamate receptor 1 (mGluR1). Moreover, the ultrastructural localization of TRPC1 was investigated by means of electron microscopy. A set of dual label experiments was also performed to investigate the presence of TRPC1 among glial cells. Our results showed that TRPC1 is localized mainly in dendritic processes of dopamine neurons, whereas a relatively small percentage of neuronal somata display a light TRPC1 immunoreactivity. Such results were confirmed by our electron microscopy observations. Our study demonstrates, for the first time, a coexpression of TRPC1 and mGluR1 receptors in dendrites of the substantia nigra dopaminergic neurons. Such observation reinforces the concept of an involvement of TRPC1 in mGluR1-mediated excitatory inputs in rat dopamine neurons.
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PMID:Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study. 1693 Apr 3

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