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)

1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 820; 3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) receptors were used to characterize the spinal effect of SP on renal function. 2. Saline gavage (4.5% of the body weight) enhanced renal excretion of water, sodium and potassium over the subsequent hour of measurement. Whereas these renal responses were not affected by 0.65 nmol SP, the dose of 6.5 nmol SP blocked the natriuretic response (aCSF value 3.9 +/- 0.8; SP value 0.7 +/- 0.3 micromol min(-1), P<0.01) as well as the renal excretion of water (aCSF value 48.9 +/- 5.8; SP value 14.5 +/- 4.0 microl min(-1), P<0.01) and potassium (aCSF value 4.8 +/- 0.6; SP value 1.5 +/- 0.6 micromol min(-1), P<0.01) at 30 min post-injection. SP had no significant effect on urinary osmolality. The SP-induced renal inhibitory effects during the first 30 min were abolished in rats subjected to bilateral renal denervation 1 week earlier or in rats injected i.t. 5 min earlier with 6.5 nmol RP 67580. In contrast, the co-injection of SR 48968 and R 820 (6.5 nmol each) did not affect the inhibitory responses to SP. On their own, these antagonists had no direct effect on renal excretion function. Since SP induced only transient changes in mean arterial blood pressure (-18.8 +/- 3.8 mmHg at 1 min and +6.3 +/- 2.4 mmHg at 5 min post-injection), it is unlikely that the renal effects of SP are due to systemic haemodynamic changes. 3. NKA (6.5 nmol but not 0.65 nmol) produced a transient drop in renal excretion of water (aCSF value 31.2 +/- 5.1; NKA value 11.3 +/- 4.2 microl min(-1), P<0.05), sodium (aCSF value 1.7 +/- 0.8; NKA value 0.4 +/- 0.2 micromol min(-1), P<0.05) and potassium (aCSF value 4.1 +/- 0.7; NKA value 1.5 +/- 0.4 micromol min(-1), P<0.05) at 15 min post-injection. However, the same doses (6.5 nmol) of selective agonists for tachykinin NK2 ([beta-Ala8]NKA(4-10)) and NK3 ([MePhe7]NKB) receptors were devoid of renal effects. 4. This study provided functional evidence that tachykinins may be involved in the renal control of water and electrolyte excretion at the level of the rat spinal cord through the activation of NK1 receptors and the sympathetic renal nerve.
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PMID:Renal effects of intrathecally injected tachykinins in the conscious saline-loaded rat: receptor and mechanism of action. 924 50

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.
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PMID:Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder. 972 57

Peripheral injury produces long term changes in peptide content in dorsal root ganglion (DRG) cells that contribute to the inflammatory process in the periphery and neuronal plasticity in the spinal cord. We report here the proportion of colonic afferents labeled for calcitonin gene-related peptide (CGRP), substance P (SP) or somatostatin (Som) in the T13-L2 and L6-S2 DRG and changes in the percentage of SP or CGRP labeled afferents 6, 24, and 72 h following induction of experimental colitis. Following injection of fluorogold (FG) into the descending colon, significantly more FG labeled DRG cells were observed in the T13-L2 than L6-S2 DRG. In noninflamed rats, in both spinal regions, 60-70% of the colonic afferents that were labeled with FG were double labeled for SP. Similar results were obtained when double labeling for CGRP. Only 20-30% of the FG labeled afferents were double labeled for Som. Following experimental colitis induced by intracolonic zymosan, there was a significant decrease in the percentage of cells double labeled for SP in the T13-L2 and L6-S2 DRG at 6, 24, and 72 h. The percentage of CGRP double labeled cells was decreased in the T13-L2 DRG at all time points, but only at 24 h in the L6-S2 DRG. The cell bodies of CGRP labeled colonic afferents were significantly larger than SP or Som in control rats. Inflammation did not affect the mean size of the double labeled cells. These results suggest that colonic inflammation increases SP and CGRP release in the spinal cord and the colon that is manifest as a decrease in peptide content in the cell bodies of the colonic afferents during the first 72 h following injury.
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PMID:The peptide content of colonic afferents decreases following colonic inflammation. 1042 83

The rat L5/6 facet joint is innervated from L1 to L6 by the dorsal root ganglia (DRG). The presence of substance P- and calcitonin gene-related peptide-immunoreactive (ir) DRG neurons innervating the L5/6 facet joint has been demonstrated. However, the presence of brain-derived neurotrophic factor (BDNF)-ir and the vanilloid receptor subtype 1 (VR1)-ir DRG neurons, which relate to inflammatory and burning pain innervating the L5/6 facet joint, has not. Fluoro-gold (FG)-labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs from T13 to L6 levels. Of the FG-labeled neurons, the proportions of BDNF-ir in L1, L2, L3, L4 and L5 DRG neurons were 9%, 15%, 21%, 17% and 20% and the proportions of VR1-ir L1, L2, L3, L4 and L5 DRG neurons were 8%, 9%, 15%, 16% and 15%, respectively.
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PMID:Brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats. 1177 2

The rat L5/6 disc is innervated from T13 to L6 dorsal root ganglia (DRGs) multisegmentally. Sensory fibers from T13, L1 and L2 DRGs have been reported to innervate through the paravertebral sympathetic trunks, whereas those from L3 to L6 DRGs innervate directly through sinuvertebral nerves on the posterior longitudinal ligament (PLL). The presence of substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive (ir) nerve fibers has been demonstrated in the lumbar intervertebral discs, but their percentages in DRG neurons have not been studied. Fluoro-gold (F-G) labeled neurons innervating the L5/6 disc were distributed throughout DRGs from T13 to L6 levels. Of F-G labeled neurons innervating the L5/6 disc, the percentage of SP-ir T13 to L6 DRG neurons was 30%, and that of CGRP-ir neurons was 47%. The mean cross-sectional area of the cell of SP-ir neurons was 696+/-66 microm2 (mean +/- S. E.), and that of CGRP-ir neurons was 695+/-72 microm2 (mean +/- S. E.). SP- and CGRP-ir were mainly observed in small neurons. The percentages of SP- or CGRP-ir neurons in L1 and L2 DRGs innervating the L5/6 disc were not different from those in L3, L4 or L5 DRGs. In the physiological condition in rats, DRG neurons at all levels may have the same significant role in pain sensation of the disc.
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PMID:Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar intervertebral discs in rats. 1205 53

The clinical benefits of intravesical electrical stimulation (IVES) in patients with increased residual urine or reduced bladder capacity have been reported. However, studies on the underlying mechanism of IVES has been limited to the Adelta afferent and parasympathetic neurons. This study investigated the changes in the calcitonin gene-related peptide (CGRP), substance P (SP), and nitric oxide synthase (NOS) expression in the thoracolumbar and lumbosacral dorsal root ganglia (DRG) of spinalized rats to determine the effect of IVES on the C fiber afferent nerve. Forty Sprague-Dawley rats were divided into normal controls (n=10); IVES treated normal rats (n=10), spinalized rats (n=10), and IVES treated spinalized rats (n=10). IVES was performed for 2 weeks (5 days a week). IVES was started 3 weeks after spinalization in the spinalized animals. All animals had the DRG removed at the thoracolumbar (T13-L2) and lumbosacral (L5-S1) level. Changes in the CGRP, SP and n-NOS levels at the DRG were measured by western-blot analysis. The relative density of the CGRP and SP following spinalization was significantly higher compared to the controls in both the T13-L2 and L5-S1 DRG. However, IVES in the spinalized rat significantly decreased the relative density of the CGRP and SP compared to the rats with spinalization alone. A significant increase in the relative density of n-NOS was detected in the L5-S1 DRG following spinalization. However, the density of n-NOS was significantly lower after IVES in both the T13-L2 and L5-S1 DRGs. In conclusion, IVES significantly reduced the CGRP, SP and n-NOS levels in the DRG of spinalized rats. CGRP, SP and n-NOS are the main factors that contribute to the hyperexcitability of the micturition reflex after spinal cord injury. These results suggest that the bladder C fiber afferent is also involved in modulating the micturition reflex by IVES.
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PMID:Sensory neuronal change after intravesical electrical stimulation in spinailized rat. 1240 80

The rat L5/6 intervertebral disc is innervated by L1 to L6 dorsal root ganglia (DRGs). T13 to L2 DRGs innervate the L5/6 intervertebral disc through paravertebral sympathetic trunks, whereas L3 to L6 DRGs directly innervate through sinuvertebral nerves on the posterior longitudinal ligament. The presence of substance P (SP)-immunoreactive (ir) and calcitonin gene-related peptide (CGRP-ir) sensory nerve fibers on the lumbar intervertebral disc has been established. SP and CGRP are markers of sensory neurons mainly involved with pain perception. The existence of SP-ir and CGRP-ir DRG neurons innervating the L5/6 intervertebral disc has been also demonstrated. Brain-derived neurotrophic factor (BDNF), which exists mainly in the small DRG neurons, plays an important neuromodulatory role in inflammatory conditions. Vanilloid receptor subtype 1 (VR1) in the DRG neurons and spinal dorsal horn is a channel that appears to confer responsiveness to heat and chemical stimuli. The presence of BDNF-ir and the VR1-ir DRG neurons innervating the L5/6 intervertebral disc has not. In this study of DRG neurons innervating the L5/6 intervertebral disc, the proportions of BDNF-ir in L1, L2, L3, L4, and L5 DRG neurons were 14%, 12%, 12%, 12%, and 13% and the proportions of VR1-ir L1, L2, L3, L4, and L5 DRG neurons were 10%, 8%, 24%, 19%, and 23%, respectively. Under physiological conditions in rats these neurons may transmit inflammatory and burning pain of the L5/6 intervertebral disc.
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PMID:Existence of brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating L5/6 intervertebral discs in rats. 1256 Aug 92

Little is known about transmitters that encode noxious gastric stimuli in the spinal cord. The release of glutamate, substance P, and CGRP from the spinal cord was therefore investigated in response to acid injury of the gastric mucosa. Dorsal halves of the caudal thoracic spinal cord (T7-T13) were removed 6 h after oral application of 0.5 M HCl or saline, transferred to a superfusion chamber, and the basal and capsaicin-stimulated (3.3 microM) transmitter release was determined. After acid injury, basal glutamate release increased 134% as compared to saline-treated animals. Capsaicin-stimulated release of CGRP and SP was 48% and 58% lower in acid- than in saline-treated animals, indicating that capsaicin-sensitive fibers in the dorsal spinal cord were already partially depleted by acid treatment. Capsaicin denervation reduced basal glutamate release by 33% after acid injury as compared to non-denervated acid-treated animals. Gastric origin and capsaicin sensitivity of glutamatergic, CGRP- and SP-containing primary afferents in thoracic dorsal root ganglia were then determined by retrograde tracing with True Blue and immunohistochemical labeling with the vanilloid receptor TRPV1. About 65% of True Blue-labeled cells were glutamatergic and more than 73% of this population expressed the TRPV1 receptor. Nearly all True Blue/CGRP (85%)- and True Blue/SP-positive cells (97%) coexpressed TRPV1. We conclude that noxious gastric stimulation with acid induces release of glutamate, SP, and CGRP from capsaicin-sensitive sensory afferents in the dorsal horn of the spinal cord where they may play an important role in gastric nociception and hyperalgesia.
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PMID:Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation. 1578 Oct 52

Intestinal inflammation is a painful syndrome with multiple symptoms, including chronic pain. This study examined the possible role of sensory neurons and substance P in symptoms of an animal model of acute intestinal inflammation. The model was induced by injecting ethanol and zymosan into the colon of anesthetized male rats. Three hours later, sections of the colon were stained with hematoxylin and eosin. To determine the role of substance P, 5 mg/kg of the neurokinin-1 receptor (NK-1r) antagonist, CP-96,345, or 300 microg/kg of an antisense oligonucleotide targeted at NK-1r mRNA was administered. Spinal cord sections were examined for internalization of NK-1r, as an indicator of substance P release. Sections of colon revealed infiltration of inflammatory cells following ethanol and zymosan treatment. Plasma extravasation in rats given ethanol and zymosan was significantly greater than in controls given saline only (P<0.0001) or saline and ethanol (P<0.001). In ethanol- and zymosan-treated rats given CP-96,345, plasma extravasation was significantly less than in rats given ethanol and zymosan without the antagonist (P<0.0001). Administration of the antisense oligonucleotide also resulted in lower levels of plasma extravasation compared with controls (P<0.01). Internalization of the NK-1r was observed in neurons of lamina I in the T13-L2 and L6-S2 regions of the spinal cord, as well as in sympathetic preganglionic neurons at the L1 level. This internalization was observed in the absence of any other stimulus besides the inflammation itself. This study implicates substance P and its receptor, the NK-1r, in acute inflammation of the colon.
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PMID:Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation. 1725 69


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