Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide substance P is known to have mnemogenic and reinforcing actions and can exert neurotrophic and regenerative effects in vitro as well as in vivo. Furthermore, our previous work in the rat showed that either pre- or post-lesion treatment with substance P can promote functional recovery in cases of partial nigrostriatal dopamine lesions. Other work has provided evidence that the effects of substance P might be differentially encoded by its C- and N-terminal fragments. The C-terminal fragment was found to be reinforcing, whereas the mnemogenic as well as neurotrophic properties have been ascribed to the N-terminal sequences. Given these relations, we asked here whether pre-lesion treatment with either a C- or an N-terminal fragment of substance P might differentially affect the behavioral and neurochemical outcome of nigrostriatal dopamine lesions. Therefore, either substance P1-7 or substance P5-11 (37 nmol/kg each) was administered intraperitoneally daily for eight consecutive days before unilateral 6-hydroxy-dopamine lesions of the substantia nigra. Control rats received pre-lesion treatment with vehicle. Furthermore, we investigated the effects of pre-treatment with Boc-cholecystokinin-4 (0.91 nmol/kg), as we had found an increase in dopamine metabolism in animals that were pre-treated with cholecystokinin-8 in a former study. In accordance with our previous work, drug treatment effects were observed when excluding animals with most severe dopamine lesions: In animals with partial lesions (residual neostriatal dopamine levels of more than 10%), lesion-dependent asymmetries in turning behavior were observed in animals that were pre-treated with vehicle-, substance P1-7, or Boc-cholecysto-kinin-4, whereas turning after pre-treatment with substance P5-11 was not significantly asymmetrical. Furthermore, the ipsi- and contra-lateral neostriatal dopamine levels did not differ significantly in this group. Moreover, pre-treatment with substance P5-11 affected dopamine metabolism in the neostriatum and in the ventral striatum, as indicated by increased ratios of dihydroxyphenyllic acid to dopamine. The data provide the first evidence that the promotive effects of substance-P treatment in the unilateral dopamine lesion model might be mediated by its C-terminal and might depend on actions on residual dopamine mechanisms.
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PMID:Pretreatment with fragments of substance-P or with cholecystokinin differentially affects recovery from sub-total nigrostriatal 6-hydroxydopamine lesion. 1071 62

The lateralis medialis-suprageniculate nuclear (LM-Sg) complex of the cat's posterior thalamus receives a rather wide variety of inputs from diverse cortical and subcortical areas. Previous ultrastructural studies of this nucleus demonstrated the presence of four types of vesicle-containing profiles and characterized some of these as gamma-aminobutyric acid (GABA)-containing terminals (Norita and Katoh [1987] J. Comp. Neurol. 263:54-67; Norita and Katoh [1988] Prog. Brain Res. 75:109-118). The present study has extended these observations by examining the immunoreactivity (ir) of LM-Sg, with antibodies raised against aspartate (Asp), glutamate (Glu), GABA, the acetylcholine (ACh) marker, choline acetyltransferase (ChAT), and substance P (SP), by using light and electron microscopy. Neuronal somata immunopositive for the excitatory amino acids (EAAs) Asp and Glu, were of medium size. EAA-ir terminals also were of medium size and contained round synaptic vesicles; they made asymmetrical synaptic contacts with dendritic profiles. Neuronal somata immunopositive for GABA were small. GABA-positive terminals also were small and contained pleomorphic synaptic vesicles; they formed symmetrical synaptic contacts with dendritic profiles. No neurons immunolabeled for ChAT were found. Terminals immunopositive for ChAT were small and contained round synaptic vesicles; these made symmetrical synaptic contacts, asymmetrical synaptic contacts, or both, of the en passant type with dendritic profiles. SP-immunolabeled neuronal somata were not found. Immunolabeled terminals were small, contained round synaptic vesicles, and made asymmetrical synaptic contacts with dendritic profiles. ChAT-ir and SP-ir axon terminals were not expressed evenly within LM-Sg. This difference in distribution suggests that within the LM-Sg, there may be a difference in specific sensory processing functions which correlate with transmitter type.
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PMID:Ultrastructural organization of transmitters in the cat lateralis medialis-suprageniculate nucleus of the thalamus: an immunohistochemical study. 1072 3

1 In cultured porcine coronary artery endothelial cells, we have recently shown that substance P and bradykinin stimulated different types of Ca(2+)-dependent K(+) (K(Ca)) current. A large part of this current was insensitive to iberiotoxin and apamin. The aim of the present study was to characterize the K(Ca) channel responsible for this current. 2 In cell-attached configuration and asymmetrical K(+) concentration, 100 nM bradykinin or substance P activated a 10 pS K(+) channel. In inside-out configuration, the channel was half-maximally activated by 795 nM free Ca(2+). 3 Apamin (1 micro M) added to the pipette solution failed to inhibit the channel activity while charybdotoxin (50 nM), completely blocked it. Perfusion at the intracellular face of the cell, of an opener of intermediate conductance K(Ca) channel, 500 micro M 1-ethyl-benzimidazolinone (1-EBIO) increased the channel activity by about 4.5 fold. 4 In whole-cell mode, bradykinin and substance P stimulated an outward K(+) current of similar amplitude. Charybdotoxin inhibited by 75% the bradykinin-induced current and by 80% the substance P-induced current. Charybdotoxin plus iberiotoxin (50 nM each) inhibited by 97% the bradykinin-response. Charybdotoxin plus apamin did not increase the inhibition of the substance P-response obtained in the presence of charybdotoxin alone. 5 1-EBIO activated a transient outward K(+) current and hyperpolarized the membrane potential by about 13 mV. Charybdotoxin reduced the hyperpolarization to about 3 mV. 6 Taken together these results show that bradykinin and substance P activate a 10 pS K(Ca) channel, which largely contributes to the total K(+) current activated by these agonists. Despite its small conductance, this channel shares pharmacological characteristics with intermediate conductance K(Ca) channels.
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PMID:Charybdotoxin-sensitive small conductance K(Ca) channel activated by bradykinin and substance P in endothelial cells. 1216 54

Cholinergic interneurons are the only known source of acetylcholine in the rat nucleus accumbens (nAcb); yet there is little anatomical data about their mode of innervation and the origin of their excitatory drive. We characterized the cholinergic and thalamic innervations of nAcb with choline acetyltransferase (ChAT) immunocytochemistry and anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) from the midline/intralaminar/paraventricular thalamic nuclei. The use of a monoclonal ChAT antiserum against whole rat ChAT protein allowed for an optimal visualization of the small dendritic branches and fine varicose axons of cholinergic interneurons. PHA-L-labeled thalamic afferents were heterogeneously distributed throughout the core and shell regions of nAcb, overlapping regionally with cholinergic somata and dendrites. At the ultrastructural level, several hundred single-section profiles of PHA-L and ChAT-labeled axon terminals were analyzed for morphology, synaptic frequency, and the nature of their synaptic targets. The cholinergic profiles were small and apposed to various neuronal elements, but rarely exhibited a synaptic membrane specialization (5% in single ultrathin sections). Stereological extrapolation indicated that less than 15% of these cholinergic varicosities were synaptic. The PHA-L-labeled profiles were comparatively large and often synaptic (37% in single ultrathin sections), making asymmetrical contacts primarily with dendritic spines (>90%). Stereological extrapolation indicated that all PHA-L-labeled terminals were synaptic. In double-labeled material, some PHA-L-labeled terminals were directly apposed to ChAT-labeled somata or dendrites, but synapses were never seen between the two types of elements. These observations demonstrate that the cholinergic innervation of rat nAcb is largely asynaptic. They confirm that the afferents from midline/intralaminar/paraventricular thalamic nuclei to rat nAcb synapse mostly on dendritic spines, presumably of medium spiny neurons, and suggest that the excitatory drive of nAcb cholinergic interneurons from thalamus is indirect, either via substance P release from recurrent collaterals of medium spiny neurons and/or by extrasynaptic diffusion of glutamate.
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PMID:Cholinergic innervation and thalamic input in rat nucleus accumbens. 1877 52

Cocaine- and amphetamine-regulated transcript (CART) peptides have been implicated in spinal pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. We demonstrated previously that the majority of these fibres originate from nociceptive primary afferents. Using tract tracing, multiple immunofluorescent labelling and electronmicroscopy we determined the proportion of peptidergic primary afferents expressing CART, looked for evidence for coexistence of CART with galanin in these afferents in lamina I and examined their targets. Almost all (97.9%) randomly selected calcitonin gene-related peptide (CGRP)-immunoreactive terminals were substance P (SP)-positive (+) and CART was detected in approximately half (48.6%) of them. Most (81.4%) of the CGRP/SPergic boutons were galanin+ and approximately half (49.0%) of these contained CART. Many (72.9%) of the CARTergic boutons which expressed CGRP were also immunoreactive for galanin, while only 8.6% of the CARTergic terminals were galanin+ without CGRP. Electron microscopy showed that most of the CART terminals formed asymmetrical synapses, mainly with dendrites. All different morphological and neurochemical subtypes of spinoparabrachial projection neurons in the lamina I received contacts from CART-immunoreactive nociceptive afferents. The innervation density from these boutons did not differ significantly between either the different neurochemical or the morphological subclasses of these cells. This suggests a nonselective innervation of lamina I projection neurons from a subpopulation of CGRP/SP afferents containing CART peptide. These results provide anatomical evidence for involvement of CART peptide in spinal pain transmission.
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PMID:Nonselective innervation of lamina I projection neurons by cocaine- and amphetamine-regulated transcript peptide (CART)-immunoreactive fibres in the rat spinal dorsal horn. 1949 82

Recently, we have demonstrated that the exposure of Wistar rats to psycho-social stress results in a transient auditory hypersensitivity. Here, to learn more about modifications occurring in auditory brainstem, we have analyzed gene expression pattern in inferior colliculus using quantitative RT-PCR. As targets, we have chosen genes associated with: neural activity (FBJ osteosarcoma viral oncogene, cFos), hypoxia (nitric oxide synthase inducible, iNos; superoxide dismutase 2, Sod2), neuroprotection (nerve growth factor beta, Ngfb; heat shock factor 1, Hsf1; heat shock protein 70, Hsp70) and inflammation (tumor necrosis factor alpha, Tnfa; tumor necrosis factor alpha receptor, Tnfar; substance P, Sp; cyclooxygenase 2, Cox2). We found that the expression of all genes was modified following stress, as compared to the controls. Immediately after stress, the number of transcripts encoding iNos, Sod2, Hsf1, Ngfb, Tnfa, Tnfar and Sp was significantly increased, suggesting possible modulation during exposure to stressor. Interestingly, we found that expression of Hsf1 and Ngfb at this particular time was left-right asymmetrical: there were more transcripts of both genes found in the left colliculi, as compared to the right colliculi. Three hours post-stress, iNos, Hsf1, Tnfa and Tnfar were still upregulated, Sod2, Ngfb and Sp went back to baseline and Cox2 was upregulated. Six hours post-stress, cFos mRNA became downregulated. The number of Hsp70 mRNA increased 24h post-stress. Except for the reduced number of cFos transcripts, expression of all other genes tested reached the baseline seven days post-stress. Presented results corroborate the concept of auditory system responding to the psycho-social stress. Post-stress changes in the IC gene expression could likely indicate shift from allostasis to homeostasis in the auditory brainstem.
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PMID:Exposure of Wistar rats to 24-h psycho-social stress alters gene expression in the inferior colliculus. 2292 17

Hypothalamic orexin/hypocretin neurons send long axonal projections through the dorsal spinal cord in lamina I-II of the dorsal horn (DH) at the interface with the peripheral nervous system (PNS). We show that in the DH OXA fibers colocalize with substance P (SP) positive afferents of dorsal root ganglia (DRG) neurons known to mediate sensory processing. Further, OR1 is expressed in p75(NTR) and SP positive DRG neurons, suggesting a potential signaling pathway between orexin and DRG neurons. Interestingly, DRG sensory neurons have a distinctive bifurcating axon where one branch innervates the periphery and the other one the spinal cord (pseudo-unipolar neurons), allowing for potential functional coupling of distinct targets. We observe that OR1 is transported selectively from DRG toward the spinal cord, while OXA is accumulated retrogradely toward the DRG. We hence report a rare situation of asymmetrical neuropeptide receptor distribution between axons projected by a single neuron. These molecular and cellular data are consistent with the role of OXA/OR1 in sensory processing, including DRG neuronal modulation, and support the potential existence of an OX/HCRT circuit between CNS and PNS.
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PMID:Orexin A and orexin receptor 1 axonal traffic in dorsal roots at the CNS/PNS interface. 2457 57


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