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

L-Homocysteic acid (L-HCA) is a sulfated amino acid which is present in mammalian striatum and is a putative excitatory striatal neurotransmitter. In the present study we examined the histologic and neurochemical effects of L-HCA induced striatal lesions to determine how closely changes resemble those of Huntington's disease (HD). Increasing doses of L-HCA injected into the anterior striatum resulted in dose-dependent reductions in both substance P-like immunoreactivity (SP-LI) and gamma-aminobutyric acid (GABA) while there was a relative sparing of both somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI). Immunocytochemical studies showed a relative sparing of NADPH-diaphorase neurons (which colocalize with SS and NPY) within regions in which there was a significant depletion of enkephalin stained neurons. The lesions were blocked by pretreatment with MK-801, a systemically effective non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors or coinjection of equimolar concentrations of 2-amino-5-phosphonovalerate (APV). These findings are similar to those produced with the NMDA agonist quinolinic acid, and suggest that other endogenous NMDA agonists, such as L-HCA, could be potential excitotoxins in HD.
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PMID:Homocysteic acid lesions in rat striatum spare somatostatin-neuropeptide Y (NADPH-diaphorase) neurons. 168 75

Microinjections of the substance P (SP) antagonist (D-pro2,D-phe7,D-trp9)-SP, or the gamma-aminobutyric acid (GABA) agonist, muscimol, into the entopeduncular nucleus reduced muscle tone in genetically spastic rats in a dose- and time-dependent manner. Similar injections into the ventral thalamus, zona incerta or amygdala had no effect on muscle tone. The muscle relaxant effect of (D-pro2,D-phe7,D-trp9)-SP injected into the entopeduncular nucleus was blocked by co-injections of SP, and that of muscimol by the GABAA antagonist, bicuculline methiodide. These results suggest that SP- and GABA-dependent mechanisms in the entopeduncular nucleus mediate regulation of the muscle tone.
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PMID:The entopeduncular nucleus regulates muscle tone in genetically spastic rats: role of substance P and gamma-aminobutyric acid. 169 Oct 40

This review summarized some articles on the effect of the septal area in acupuncture analgesia. The data showed that the pain threshold of animal was increased when septal area was stimulated by electro-acupuncture, and that electrical stimulation of septal area had a marked inhibitory effect on the pain discharges of cells in parafascicular nucleus of thalamus, lateral habenular nucleus, periaqueductal gray and dorsal raphe nucleus. The septal area play an important role in acupuncture analgesia. The majority of the cholinergic neurons in septal area are located in nucleus of the vertical limb of the diagonal band (VDB); gamma-aminobutyric acid of septal area is mainly found in the diagonal band nucleus(td); Dopamine is present in high levels in td and lateral septal nucleus(S1) of septal area; The S1 contain high densities enkephalin-containing neuronal cell bodies and terminals; In addition, substance P and norepinephrine are also high levels in the septal area. These substance above-mentioned have a relations with acupuncture analgesia of septal area. A large number of serotonin-containing neurons are found in the raphe nuclei. The serotonin play an important role in acupuncture analgesia. The serotonin-containing neurons in dorsal raphe nucleus project to S1. The fiber connections of the raphe nuclei with the td are reciprocation. The periaqueductal gray is a important structure on pain modulation. It projects to septal area and receives the fibers from S1. A number of adrenergic neurons are located within the locus coeruleus. The locus coeruleus participate pain modulation and acupuncture analgesia. The neuro-anatomy study demonstrated that locus coeruleus projects to septal area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of the septal area in acupuncture analgesia]. 169 24

A depletion of large cholinergic neurons in the nucleus basalis of Meynert is a consistent finding in Alzheimer's disease (AD). The nucleus basalis of Meynert also contains interneurons and afferents that may modulate its functioning. In the present study we examined neurochemical markers for neuropeptides, amino acid neurotransmitters, and monoaminergic neurotransmitters in postmortem samples of the nucleus basalis in 16 control subjects and 30 patients with AD. There were no significant changes in glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and catecholamines; however, concentrations of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol were significantly reduced. Choline acetyltransferase activity was significantly reduced, consistent with previous reports. Galanin immunoreactivity was significantly increased twofold in the patients with AD, but there were no significant changes in substance P, somatostatin, or neuropeptide Y immunoreactivity. Since galanin inhibits acetylcholine release, and produces cognitive deficits in animals, increased galanin immunoreactivity in the nucleus basalis of Meynert in AD may contribute to the cognitive deficits that characterize the illness.
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PMID:Galanin immunoreactivity is increased in the nucleus basalis of Meynert in Alzheimer's disease. 169 71

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.
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PMID:Pain and neurotransmitters. 170 58

In order to examine the synaptic input to dopaminergic neurones in the substantia nigra from GABAergic terminals and terminals that contain substance P, double and triple immunocytochemical studies were carried out at the light and electron microscopic levels in the rat. In a first series of experiments sections of the substantia nigra were incubated to reveal axon terminals containing either substance P or glutamate decarboxylase and then incubated to reveal dopaminergic neurones using tyrosine hydroxylase immunocytochemistry. Examination of this material in the light microscope revealed that many substance P- and glutamate decarboxylase-immunoreactive boutons were associated with the dopaminergic cells. In the electron microscope it was found that the perikarya and dendrites of the dopaminergic neurons received symmetrical synaptic input from terminals that displayed immunoreactivity for substance P or glutamate decarboxylase. A small proportion of the substance P-positive boutons formed asymmetrical synapses. In a second series of experiments sections of the substantia nigra were processed by the pre-embedding immunocytochemical technique for tyrosine hydroxylase and then the post-embedding immunogold technique for gamma-aminobutyric acid (GABA). Examination in the electron microscope revealed that the tyrosine hydroxylase-positive neurons received symmetrical synaptic input from many GABA-positive terminals. Quantitative analyses demonstrated that a minimum of 50-70% of all boutons afferent to the dopaminergic neurones display glutamate decarboxylase or GABA immunoreactivity. Triple immunocytochemical studies i.e. pre-embedding immunocytochemistry for tyrosine hydroxylase and substance P, combined with post-embedding immunogold staining for GABA, revealed that some of the substance P-immunoreactive boutons that were in contact with the dopaminergic neurones also displayed GABA immunoreactivity. In a third series of experiments the combination of anterograde transport of lectin-conjugated horseradish peroxidase or biocytin with post-embedding GABA immunocytochemistry demonstrated that at least one of the sources of GABA-containing terminals in the substantia nigra is the striatum. The results of the present study: (1) demonstrate that dopaminergic neurones in the substantia nigra receive symmetrical synaptic input from GABAergic and substance P-containing terminals, (2) show that a proportion of these terminals contain both substance P and GABA and (3) suggest that the major synaptic input to dopaminergic neurones is from GABAergic terminals and that a part of this innervation is derived from the striatum.
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PMID:The GABA and substance P input to dopaminergic neurones in the substantia nigra of the rat. 170 87

Immunocytochemical studies of the vestibular nuclei (VN) were done in the squirrel monkey and cat using polyclonal antisera. Brain stem sections were processed using the Avidin-Biotin peroxidase complex with diaminobenzidine as the chromagen. Choline acetyltransferase immunoreactivity (ChAT-IR) was most prevalent in the caudal medial (MVN), inferior (IVN) and peripheral superior (SVN) VN. Nearly all cells of groups x and z were ChAT-positive. None of the giant cells of the lateral vestibular nucleus (LVN) was ChAT-IR. Glutamate immunoreactivity (GLU-IR) was abundant in all VN and in cells of the vestibular ganglion (VG). Gamma-aminobutyric acid immunoreactivity (GABA-IR), was found in cells of rostral MVN, cell group y and in granules about giant cells in dorsal LVN. Substance P immunoreactive (SP-IR) was present in a small cells in MVN, IVN and the VG and in granules surrounding all large cells in LVN in both monkey and cat; SP-IR granules were most intense in ventral LVN in the monkey. Some cells in the dorsal parts of the fastigial nucleus (FN) were outlined by SP-IR granules in both species. Leucine-enkephalin immunoreactivity (ENK-IR) was identified only in granules surrounding cells of group x in the monkey. GLU was the only immunoreactive substance found in the giant cells of LVN. The disposition of ChAT-IR in the VN suggested participation in commissural systems, as well as projections to spinal cord and/or cerebellum. Small GABA-IR neurons in MVN probably represented both commissural and projection neurons; GABA-IR granules about cells in dorsal LVN and some cells in MVN and SVN appeared to represent Purkinje cell (PC) terminals. SP-IR granules surrounding cells in ventral LVN appeared to represent terminals of small SP-positive VG cells. The source of SP-IR granules around cells in dorsal LVN and some cells in FN and SVN remains unknown, but these fibers may originate from portions of the reticular formation known to contain large numbers of SP-positive neurons.
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PMID:Immunocytochemical features of the vestibular nuclei in the monkey and cat. 170 74

Retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was studied in 7 squirrel monkeys with discrete injections of the subthalamic nucleus (STN). Injections labeled: (1) the lateral two-thirds of the nucleus (63% and 47%), (2) ventrolateral parts caudally (20%), (3) dorsomedial parts caudally (18%), (4) rostromedial parts (21%), (5) the medial third (38%) and (6) the lateral pole of the nucleus (9%). Afferents to the lateral two-thirds of the STN originated from two parallel cellular arrays in dorsal parts of the middle third of the lateral pallidal segment (LPS) and a single array in the rostral third of the LPS. Medial regions of the STN received input from cells in the rostral LPS. Small numbers of cells were retrogradely labeled in the centromedian-parafascicular (CM-PF) and the pedunculopontine (PPN) nuclei. No cells were labeled in the frontal cortex, the striatum, the substantia innominata (SI), the substantia nigra (SN) or the dorsal nucleus of the raphe. Virtually all pallidal neurons, including identified pallidosubthalamic neurons, were immunoreactive (IR) for gamma-aminobutyric acid (GABA). Pallidosubthalamic neurons were most numerous in regions of the LPS with the lowest density of leucine enkephalin-IR fibers. Substance P-IR fibers, found mainly in the medial pallidal segment, bore no relationship to pallidal afferents to the STN. Choline acetyltransferase-IR cells in the SI and the PPN were not retrogradely labeled with WGA-HRP granules. Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS, suggesting a reciprocal relationship. The caudal third of the LPS and ventral region of the middle third of this nucleus, appeared to project few fibers to, or to receive few fibers from, the STN. A small number of STN efferents entered the medial border of the putamen, but no terminal fields were identified. STN projections to the pars reticulata of the SN appeared to represent about 10% of the projection to the LPS. No STN efferents were identified in the frontal cortex, the SI or the PPN. The hypothesis that STN afferents from the frontal cortex and CM-PF may represent collaterals of projections to other loci is discussed.
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PMID:Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents. 170 79

The levels of extracellular striatal dopamine and glutamate were measured simultaneously in halothane-anaesthetized rats using microdialysis. Unilateral injections of substance P (0.07 nmol) into the substantia nigra, pars reticulata enhanced the levels of dopamine and glutamate in the ipsilateral striatum. Intranigral injections of neurokinin A (0.09 nmol) enhanced the levels of striatal dopamine, and intranigral injections of gamma-aminobutyric acid (300 nmol) or dynorphin A (0.5 nmol) decreased the levels of striatal dopamine, but none of these had any effect on the levels of striatal glutamate. Local perfusion with the dopamine agonists apomorphine (D1/D2), SKF 38393 (D1) or pergolide (D2) (each at 10(5) M) decreased the levels of striatal dopamine and enhanced the levels of striatal glutamate. In unilateral 6-hydroxydopamine-lesioned rats, basal striatal glutamate levels were decreased bilaterally. Furthermore, on the denervated side intranigral substance P stimulation of striatal glutamate levels was enhanced, while on the intact side intranigral substance P stimulation of striatal dopamine and glutamate levels was similar to that seen in normal rats. These findings suggest that striatonigral substance P provides a stimulatory regulation of ipsilateral striatal glutamate release. Furthermore, it is indicated that striatal glutamate release can also be regulated by dopamine terminals.
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PMID:Striatal dopamine and glutamate release: effects of intranigral injections of substance P. 170 11

Areas 20, 21 and 22 of the temporal neocortex of the macaque monkey (Macaca fascicularis) were studied with immunocytochemical and electron-microscopic techniques to localise neurons immunoreactive to the neuropeptides vasoactive intestinal polypeptide, substance P and somatostatin, and to gamma-aminobutyric acid (GABA). GABAergic neurons were found in all cortical layers, but especially in layers II, IV and VI. They were all of non-pyramidal morphology, comprising small round cells, and bipolar or multipolar forms. Presumed GABAergic axon terminals were also common. Peptidergic neurons were also found in all layers, but they consisted of cells of many morphological types, including pyramidal cells. Compared with previous descriptions in other cortical areas and in other animals, we find a greater proportion of peptidergic temporal cortical neurons compared to the GABAergic population. The immunopositive neurons were easily recognisable ultrastructurally from non-reactive neurons by the dense labelling of the cytoplasm and nucleus. Immunopositive and negative neuronal somata were often contiguous, providing evidence for the specificity of the immune reaction. Stem dendrites were often labelled for a short distance from the soma, and other strongly reacting dendritic segments were found in the neuropil, as were labelled axons. Neurons labelled for GABA had features typical of non-pyramidal cells, but neuropeptides were also found in cells with pyramidal characteristics.
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PMID:Pyramidal neurons are immunopositive for peptides, but not GABA, in the temporal cortex of the macaque monkey (Macaca fascicularis). 170 16


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