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)

Primary afferent terminals in the dorsal horn of the spinal cord release excitatory amino acid and peptide transmitters that initiate the central processing of nociceptive information. The postsynaptic actions of amino acid transmitters on spinal neurons have been well characterized, but the cellular basis of peptide actions remains unclear. Substance P is the best characterized of the peptides present in sensory neurons and has been shown to depolarize dorsal horn neurons and to facilitate nociceptive reflexes. To determine the mechanisms by which substance P contributes to afferent synaptic transmission, we have monitored the levels of intracellular calcium in single isolated rat dorsal horn neurons and report that substance P can produce a prolonged elevation in calcium concentration by mobilizing its release from intracellular stores. This elevation may contribute to the long-term changes in the excitable properties of dorsal horn neurons that occur following afferent fibre stimulation. We have also found that L-glutamate elevates intracellular calcium in substance P-sensitive dorsal horn neurons by increasing calcium influx. These results provide a direct demonstration of intracellular calcium changes in response to neuropeptides in mammalian central neurons. They also indicate that there is convergent regulation of intracellular calcium in dorsal horn neurons by two different classes of sensory transmitters that are co-released from the same afferent terminals.
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PMID:Sensory transmitters regulate intracellular calcium in dorsal horn neurons. 245 71

Several neuropathologic studies have suggested that there may be pathologic involvement of the cerebellum in Huntington's disease (HD). To investigate this further, we measured concentrations of neurotransmitter amino acids and the neuropeptides, somatostatin, neuropeptide Y and substance P, in HD cerebellar cortex and dentate nucleus. Twenty-seven pathologically confirmed cases of HD were compared with 20 controls. There were no significant changes in concentrations were significantly increased by 21% in HD cerebellar cortex. In the dentate nucleus, there were small significant increases of neuropeptide Y-like immunoreactivity and substance P-like immunoreactivity. The meaning of the neurotransmitter changes found is unclear: however, the lack of change in GABA and glutamate concentrations argues against a substantial loss of intrinsic cerebellar neurons.
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PMID:Amino acid and neuropeptide neurotransmitters in Huntington's disease cerebellum. 245 9

By light microscopic immunocytochemistry it has been previously shown that approximately equal to 70% of the neurons in rat dorsal root ganglia are labeled with an antiserum for glutamate conjugated to hemocyanin; the smaller among these neurons are also positive for substance P. By using a postembedding ImmunoGold method and electron microscopy, it is shown here that synaptic terminals in the superficial laminae of the spinal cord of rats selectively stain for the same glutamate antiserum. Immunolabeling is in small dome-shaped and in large scalloped synaptic terminals. Scalloped terminals are of two types. One type consists of dark terminals with many agranular vesicles of different size and a few large granular vesicles; these are probably endings of unmyelinated and small myelinated primary afferent fibers. The other type consists of light terminals with small agranular vesicles homogeneous in size with neurofilaments and many mitochondria; these are probably endings of larger myelinated primary afferent fibers. By means of double-labeling electron microscopic immunocytochemistry with colloidal gold particles of two different sizes, it is also shown here that substance P is present in only the dark type of glutamate-labeled scalloped terminals. The primary afferent origin of the terminals labeled by the antisera for glutamate and for substance P is demonstrated by a triple-labeling strategy: immunocytochemistry for both antisera on sections from rats in which dorsal rhizotomy or dorsal root ganglion injection of horseradish peroxidase conjugated to wheat germ agglutinin was performed. It is proposed that glutamate is the neurotransmitter in primary afferents mediating input from different peripheral receptor classes, including nociceptors. Effects of glutamate and substance P on spinal dorsal horn neurons may result from co-release of these two mediators from the same dorsal root afferent terminal.
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PMID:Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. 245 17

The present investigation was prompted by previous studies in our laboratory which have indicated that tachykinins enhance depressant effects of purines and that the purine adenosine mediates a vibration-induced depression of nociceptive dorsal horn neurons. Extracellular recordings were made from single nociceptive neurons in the lower lumbar segments of anaesthetized cats. Vibration (80 Hz; 2.5-3.5 s every 20-25 s) was applied to the hindlimb using a feedback-controlled mechanical stimulator. The tachykinins physalaemin, substance P and neurokinin A were administered by iontophoresis. Physalaemin was tested on vibration-induced responses of 29 neurons; each neuron was excited by this tachykinin. To control for possible changes in the response to vibration caused by the excitation per se, statistical comparisons were made of the vibration-induced responses during excitation by tachykinins and during excitation by glutamate. In 16 cases the magnitude of the vibration-induced depression was significantly greater during the excitation caused by physalaemin. With the remaining neurons the response to vibration failed to differ during the excitation by physalaemin compared with the excitation by glutamate. In four of the 16 cases subthreshold applications of vibration caused depression after administration of physalaemin. The P1-purinergic (adenosine) antagonist, caffeine, was administered in three cases where vibration caused depression only with application of physalaemin. In each of these cases the depression was reversibly blocked by caffeine (10 or 40 mg kg-1 i.v.). The magnitude of vibration-induced depression was significantly increased during excitation by neurokinin A (5/14 neurons) or by substance P (1/9 neurons). From the results of the present study we suggest that tachykinins enhance the vibration-induced depression. This enhancement may be due to enhanced depression by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tachykinins enhance the depression of spinal nociceptive neurons caused by cutaneously applied vibration in the cat. 246 89

We have demonstrated a high affinity specific binding of 125I-Bolton Hunter conjugate of substance P (125I-BHSP) to rat retina membranes. The binding was saturable and monophasic with a Kd of 0.2 nM and a Bmax of 290 fmol/mg protein. The rank order of potency of tachykinins and related analogues in inhibiting 125I-BHSP binding conformed to that of the NK-1 (identical to SP-P) tachykinin receptor, with SP greater than NKA greater than or equal to KAS greater than or equal to NKB and [Glp6, L-Pro9]SP(6-11) being 60 times more active than [Glp6, D-Pro9]SP(6-11). After neonatal monosodium glutamate (MSG) treatment, there was a marked reduction in the number but not binding affinity of 125I-BHSP binding sites in the retina. The same treatment had no effect on either the number or binding affinities of NK-1 sites in the salivary gland.
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PMID:Effects of neonatal monosodium glutamate treatment on substance P binding sites in the rat retina. 246 98

Alzheimer's disease (AD) is one of more than 60 disorders that may produce dementia. It is characterized clinically by memory deficits and by the presence of aphaso-apracto-agnosic disorders. In the general population, AD has an incidence of 0.3 to 1% and is very common in the elderly (more than 50% of dementia cases). The pattern of pathological changes in the brain in AD is relatively specific. Neuritic plaques, neurofibrillary tangles and cell loss, occur primarily in the cerebral neocortex and hippocampus. On the other hand, neurochemical deficiencies related to the illness have now been identified. The vulnerability of the cholinergic system of the basal nucleus of Meynert was first documented. Following the discovery of the cholinergic reduction in AD and among a dozen of neurotransmitter systems involved in AD, somatostatin, substance P, neuropeptide Y, corticotropin releasing factor and amino acid glutamate were investigated and are the most affected in AD. Results of previous publications and our own investigations are presented here.
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PMID:[Neuromodulators and Alzheimer's disease]. 246

Administered intrathecally (IT) to mice, the putative substance P antagonist [D-Pro2,D-Trp7,9-substance P (DPDT) blocked substance P- and serotonin-induced reciprocal hindlimb scratching with ID50 values of 4.6 (2.9-6.9) and 3.0 (1.9-4.8) micrograms, respectively. The duration of this antagonistic effect was 90-120 min. In contrast, DPDT did not block bombesin-, somatostatin-, glycine- or glutamate-induced scratching. These data indicate that DPDT is an effective antagonist of serotonin-induced behaviors in the mouse spinal cord. Phenoxybenzamine (IT) also blocked substance P- and serotonin-induced scratching. Its onset of action was more rapid for serotonin than for DPDT implying differences in agonist-induced receptor activation. Methysergide (IT) blocked serotonin-induced scratching [ID50 = 0.7 (0.3-1.5) micrograms], but not substance P-induced scratching. Similar to DPDT, [D-Arg1,D-Trp7,9,Leu11]-substance P, [des-Arg1,D-Pro2, D-Trp7,9]-substance P(2-11) and [D-Pro4,D-Trp7,9]-substance P(4-11) blocked substance P and serotonin-induced scratching. In contrast, [D-Pro2,D-Phe7,D-Trp9]-substance P and [D-Pro4,D-Trp7,9,10]-substance P(4-11) blocked only substance P-induced scratching. Thus, some, but not all putative substance P antagonists may also be behavioral antagonists of serotonin in the mouse spinal cord.
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PMID:Interactions of substance P antagonists with serotonin in the mouse spinal cord. 246 43

Antisera to a glutamate (Glu) conjugate, to glutaminase (GLN), and to substance P (SP) have been used to investigate the issue of putative glutamergic neurons in the dorsal root ganglia (DRG) and the possible coexistence in these neurons of Glu and SP. The Glu antiserum, characterized by immunoadsorption and immunoblot tests, is highly selective for Glu out of a number of other amino acids including aspartate. Quantitative data were gathered from consecutive 4-microns-thick paraffin sections from cervical ganglia of rats with or without spinal injections of colchicine and from one monkey not treated with colchicine. Neurons containing more than one antigen could be identified on adjacent sections tested with the three different antisera. Neurons labeled by the Glu-antiserum represent 15-30% of the DRG population in untreated rats. They include most of the small neurons (with mean perikaryal area around 300-400 microns) but also larger neurons (with perikaryal area greater than 600 microns). DRG neurons labeled by either the GLN or the SP antiserum are small (mean area 335-375 microns and 356-374 microns, respectively) and account for approximately 40 and 15%, respectively, of the sampled neurons. In colchicine-treated rats the number of Glu-positive neurons increases up to about 70%. The same treatment also increases the number of SP-positive neurons but not that of GLN-positive neurons. In the monkey about half of the DRG neurons are Glu positive and, as in rats, they are mostly small. GLN-positive neurons in the same species account for about half of the DRG population and are only small. In rats, about 60-80% of Glu-positive neurons are also GLN-positive and most GLN-positive neurons are Glu positive. In colchicine-treated rats, close to 90% of SP-positive neurons are also positive for Glu and about 60% of SP-positive neurons are triple labeled. In the monkey's DRGs, whose sections were not processed for SP, most Glu- or GLN-positive neurons are also positive for the other antiserum used. Several considerations argue against the possibility that, under the present experimental conditions, the Glu antiserum is a metabolic marker. It is therefore suggested that Glu-positive neurons may use Glu as neurotransmitter. Coexistence of Glu and SP in some DRG neurons suggests that both agents may be released by terminals of primary afferents from the same DRG neuron.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Coexistence of glutamate and substance P in dorsal root ganglion neurons of the rat and monkey. 246 61

Formation of experimental neurosis in rats was accompanied in 64% of animals by development of amnesia of conditioned reaction of passive avoidance. Disturbance of mnestic processes was manifested by a change in free amino acids pool including the acids with neurotransmitter properties (GABA, glutamate, glycine). An increase of GABA and glycine content was found in the frontal cortex and an increase of glutamate and GABA--in the hippocampus and striate body. Substance P (125 mkg/kg) administered intraperitoneally against the background of a developed neurosis, produced in 80% of cases an antiamnestic action, accompanied by a statistically significant decrease of GABA content in the frontal cortex, hippocampus and midbrain, and an increase of glutamate in the midbrain. The level of taurine decreased in the frontal cortex, hippocampus and striate body, and increased in the midbrain. Threonine content increased in the striate body and midbrain; there was an increase of taurine, serine and glycine in the midbrain and of glycine in the striate body.
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PMID:[Effect of substance P on the reproduction of memory engrams and on the amino acid composition of brain structures in rats with experimental neurosis]. 246 61

In vitro studies have demonstrated that glia can express functional receptors for a variety of neurotransmitters. To determine whether similar neurotransmitter receptors are also expressed by glia in vivo, we examined the glial scar in the transected optic nerve of the albino rabbit by quantitative receptor autoradiography. Receptor binding sites for radiolabeled calcitonin gene-related peptide, cholecystokinin, galanin, glutamate, somatostatin, substance P, and vasoactive intestinal peptide were examined. Specific receptor binding sites for each of these neurotransmitters were identified in the rabbit forebrain but were not detected in the normal optic nerve or tract. In the transected optic nerve and tract, only receptor binding sites for substance P were expressed at detectable levels. The density of substance P receptor binding sites observed in this glial scar is among the highest observed in the rabbit forebrain. Ligand displacement and saturation experiments indicate that the substance P receptor binding site expressed by the glial scar has pharmacological characteristics similar to those of substance P receptors in the rabbit striatum, rat brain, and rat and canine gut. The present study demonstrates that glial cells in vivo express high concentrations of substance P receptor binding sites after transection of retinal ganglion cell axons. Because substance P has been shown to regulate inflammatory and immune responses in peripheral tissues, substance P may also, by analogy, be involved in regulating the glial response to injury in the central nervous system.
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PMID:Substance P receptor binding sites are expressed by glia in vivo after neuronal injury. 247 40


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