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)

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

The serotonergic dorsal raphe nucleus (DR) is an area enriched with cell bodies and axons containing the third vesicular glutamate transporter, VGLUT3. However, the role of VGLUT3-containing axons in modulating activity of serotonin (5-HT) neurons within the DR remains poorly understood. In this study, neurochemical features and topography of VGLUT3-containing cell bodies and axons in the DR were examined. Since many 5-HT cells have been reported to express VGLUT3, the distribution of dually labeled axons was examined within the DR. Axons containing both VGLUT3 and 5-HT immunolabeling had a topographic distribution: they innervated the ependyma and ramified within the caudal DR at the base of the aqueduct, an area known to give rise to ependymal innervation. Thus VGLUT3 is only present in a specific subcomponent of recurrent 5-HT axon collaterals. Remaining VGLUT3 axons were only rarely dually immunolabeled for markers of monoamines, GABA, or acetycholine, suggesting these axons contain a predominance of glutamate-filled vesicles. Since the substance P receptor, neurokinin 1 (NK1), has previously been associated with local glutamate neurons in the DR, the relationship between NK1, 5-HT and VGLUT3 cells was examined using triple-immunolabeling. Results indicate that the majority of non-5-HT VGLUT3-containing cell bodies in the DR contain NK1 immunolabeling. Taken together, these findings indicate locally collateralizing glutamate neurons responsive to substance P contain VGLUT3.
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PMID:Locally collateralizing glutamate neurons in the dorsal raphe nucleus responsive to substance P contain vesicular glutamate transporter 3 (VGLUT3). 1946 22

The third vesicular glutamate transporter (VGLUT3) is expressed in a subset of cholinergic and GABAergic neurons in the forebrain. In this study the distribution of VGLUT3 was mapped in relation to the receptor for substance P, neurokinin 1 (NK1), which has been independently reported within cholinergic and GABAergic neurons in a similar distribution. Dual immunofluorescence labeling techniques were used, sometimes in combination with triple labeling for the vesicular acetylcholine transporter (VAChT), to identify cholinergic cells. Virtually all cells immunolabeled for VGLUT3 in the nucleus accumbens core and shell regions, ventral pallidum, olfactory tubercle and caudate putamen were cholinergic and also contained immunolabeling for the NK1 receptor. In the hippocampal formation where VGLUT3 has been described in GABAergic neurons, colocalization between NK1 and VGLUT3 was also common but less complete. Cells double labeled for NK1 and VGLUT3 were most prevalent in stratum radiatum in the CA1 subfield. In the habenula VGLUT3 was also found within NK1 receptor immunolabeled neurons. However, there were some areas where neurons containing these two proteins were separate populations including the cerebral cortex and median raphe nucleus. These results reveal a trend for VGLUT3 to localize within neurons containing the NK1 receptor in several areas of the forebrain.
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PMID:Coincidence of neurokinin 1 receptor with the vesicular glutamate transporter 3 (VGLUT3) in the rat forebrain. 1969 79

Serotonin neurons play a major role in many normal and pathological brain functions. In the rat these neurons have a varying number of cotransmitters, including neuropeptides. Here we studied, with histochemical techniques, the relation between serotonin, some other small-molecule transmitters, and a number of neuropeptides in the dorsal raphe nucleus (DRN) and the adjacent ventral periaqueductal gray (vPAG) of mouse, an important question being to establish possible differences from rat. Even if similarly distributed, the serotonin neurons in mouse lacked the extensive coexpression of nitric oxide synthase and galanin seen in rat. Although partly overlapping in the vPAG, no evidence was obtained for the coexistence of serotonin with dopamine, substance P, cholecystokinin, enkephalin, somatostatin, neurotensin, dynorphin, thyrotropin-releasing hormone, or corticotropin-releasing hormone. However, some serotonin neurons expressed the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD). Work in other laboratories suggests that, as in rat, serotonin neurons in the mouse midline DRN express the vesicular glutamate transporter 3, presumably releasing glutamate. Our study also shows that many of the neuropeptides studied (substance P, galanin, neurotensin, dynorphin, and corticotropin-releasing factor) are present in nerve terminal networks of varying densities close to the serotonin neurons, and therefore may directly or indirectly influence these cells. The apparently low numbers of coexisting messengers in mouse serotonin neurons, compared to rat, indicate considerable species differences with regard to the chemical neuronatomy of the DRN. Thus, extrapolation of DRN physiology, and possibly pathology, from rat to mouse, and even human, should be made with caution.
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PMID:Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain. 2058 9

The dorsal raphe nucleus (DR) contains the majority of serotonin (5-hydroxytryptamine, 5-HT) neurons in the brain that regulate neural activity in forebrain regions through their widespread projections. DR function is linked to stress and emotional processing, and is implicated in the pathophysiology of affective disorders. Glutamatergic drive of the DR arises from many different brain areas with the capacity to inform the nucleus of sensory, autonomic, endocrine and metabolic state as well as higher order neural function. Imbalance of glutamatergic neurotransmission could contribute to maladaptive 5-HT neurotransmission and represents a potential target for pharmacotherapy. Within the DR, glutamate-containing axon terminals can be identified by their content of one of three types of vesicular glutamate transporter, VGLUT1, 2 or 3. Each of these transporters is heavily expressed in particular brain areas such that their content within axons correlates with the afferent's source. Cortical sources of innervation to the DR including the medial prefrontal cortex heavily express VGLUT1 whereas subcortical sources primarily express VGLUT2. Within the DR, many local neurons responsive to substance P contain VGLUT3, and these provide a third source of excitatory drive to 5-HT cells. Moreover VGLUT3 is present, with or without 5-HT, in output pathways from the DR. 5-HT and non-5-HT neurons receive and integrate glutamatergic neurotransmission through multiple subtypes of glutamate receptors that have different patterns of expression within the DR. Interestingly, excitatory drive provided by glutamatergic neurotransmission is closely opposed by feedback inhibition mediated by 5-HT1A receptors or local GABAergic circuits. Understanding the intricacies of these local networks and their checks and balances, may help identify how potential imbalances could cause psychopathology and illuminate strategies for therapeutic manipulation.
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PMID:Glutamatergic drive of the dorsal raphe nucleus. 2155 Mar 97

Injection into the nucleus tractus solitarii (NTS) of toxins that target substance P (SP) receptors ablates neurons that express neurokinin-1 (NK1) receptors, attenuates baroreflexes, and results in increased lability of arterial pressure. We and others have shown that the toxin leads to loss of neurons containing SP receptors and loss of GABAergic neurons in the NTS; but given that neither type neuron is thought to be integral to baroreflex transmission in NTS, mechanisms responsible for the cardiovascular changes remained unclear. Because NK1 receptors colocalize with N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in NTS and because glutamate transmission may be integral to baroreflex transmission in the NTS we hypothesized that the toxic lesions may interrupt mechanisms for glutamate transmission. Interruption of those mechanisms could be responsible for the cardiovascular effects. We tested the hypothesis by performing fluorescent immunohistochemistry, confocal microscopy and image analysis after injecting stabilized SP-SAP (SSP-SAP) unilaterally into the NTS. We assessed changes in immunoreactivity (IR) of NMDA receptor subunit 1 (NMDAR1), AMPA receptor subunit 2 (GluR2), and 3 types of vesicular glutamate transporters (VGluT) as well as IR of gamma-aminobutyric acid receptors type b (GABAb), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), and protein gene product 9.5 (PGP 9.5), a neuronal marker, in the NTS. When compared to that of the same section of the un-injected NTS, IR decreased significantly in the injected side for NMDAR1 (p<0.01), GluR2 (p<0.01), VGluT3 (p<0.01), GABAb (p<0.001), and PGP9.5 (p<0.001). In contrast, IR for VGluT1 (p<0.001), VGluT2 (p<0.001), nNOS (p<0.001), and TH (p<0.001) increased significantly. We conclude that pathologic effects following ablation of neurons with NK1 receptors in NTS may result from interruption of neurotransmission through other neurochemical systems associated with NK1 receptors-containing neurons.
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PMID:Collateral damage and compensatory changes after injection of a toxin targeting neurons with the neurokinin-1 receptor in the nucleus tractus solitarii of rat. 2241 22