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)

Seventy patients aged from one month to 18 years with seizure disorders were classified into three groups: I. Patients who had hard control seizure attacks even under medication; II. those who had occasional seizure attacks (less than 6 times per year) and III. those who had no seizure attacks after receiving medication for at least one year. Blood samples were taken for somatostatin, substance P, prolactin and vasoactive intestinal peptide (VIP) assays. Lumbar puncture was made in 32 children and CSF samples were also assayed for neuropeptides. Somatostatin levels in serum were significantly elevated in group I and group II (P = 0.05, ANOVA) but not in group III and control group. Similar observations were made in substance P, prolactin and VIP studies. In CSF, the somatostation can better indicate the difference between epileptic and normal children (comparison with group I, P greater than 0.001; with group II, P less than 0.001; even with those who were seizure free after medication, P less than 0.05). In conclusion, the levels of several neuropeptides (somatostatin, substance P. prolactin, VIP) were elevated in children with seizure disorders both in serum and CSF. The present investigation provides a new category for the understanding of the pathogenesis, treatment as well as prognosis of seizure disorders.
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PMID:Somatostatin, substance P, prolactin and vasoactive intestinal peptide levels in serum and cerebrospinal fluid of children with seizure disorders. 171 68

Serine proteinases participate in many inflammatory events in the airway. We therefore screened perfusates of isolated rat tracheas for tryptic, elastolytic, and chymotryptic serine proteinases. Only chymotryptic activity, indicated by hydrolysis of the synthetic substrate N-succinylalanylalanylprolylphenylalanyl p-nitroaniline (AAPF), was consistently detected in these perfusates. Basal levels of chymotryptic activity were not increased significantly by electrical field stimulation (EFS) (mean change +/- SEM: -0.05 +/- 0.05 m o.d. units, n = 4) or by 10(-7) M substance P (SP) (+0.04 +/- 0.02 m o.d. units, n = 14). However, the mean change after the stimuli were jointly administered (0.17 +/- 0.06 m o.d. units, n = 12) was significantly greater than control or after EFS (P = 0.01, one-way ANOVA). The SP + EFS-induced chymotryptic activity was inhibited by PMSF, soybean trypsin inhibitor, and chymostatin and was associated with an increase in histamine concentration and immunoreactivity to rat mast cell proteases (RMCP), indicating that the activity is due to mast cell degranulation. However, the activity was not significantly decreased by pretreating rats with systemic compound 48/80. SP + EFS-induced chymotryptic activity peaked rapidly and was associated with modest histamine release and an immediate peak in immunoreactivity to RMCP II, a marker of mucosal mast cells. Immunoreactivity to RMCP I, a marker of connective tissue mast cells, also increased after SP + EFS, but this immunoreactivity was either delayed or more sustained and did not coincide with the peak of chymotryptic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chymotryptic activity in perfusates of isolated rat trachea: correlation with mucosal and connective tissue mast cell secretion. 752 16

1. This study investigates the effects of capsaicin-induced depletion of sensory neuropeptides and of neurokinin1 (NK1) receptor blockade on delayed-type hypersensitivity (DTH)-induced changes of vascular permeability in the small intestine of the mouse. 2. The DTH reaction in the small intestine was elicited by dinitrofluorobenzene (DNFB)-contact sensitization followed by oral dinitrobenzene sulphonic acid (DNBS) challenge. To assess vascular leakage the accumulation of the plasma marker, Evans blue (EB), was measured 2, 24 and 48 h after the challenge. 3. The small intestinal DTH reaction was characterized by a significant increase in vascular permeability 24 h after the challenge of previously sensitized mice when compared to vehicle-sensitized mice (P < 0.05, ANOVA). Capsaicin-induced depletion of sensory neuropeptides, two weeks before the sensitization, completely inhibited the DTH-induced increase in small intestinal vascular permeability at 24 h (P < 0.05, ANOVA). Vehicle/control: 108.2 +/- 8.6 ng EB mg-1 dry weight; vehicle/DTH 207.8 +/- 25.1 ng EB mg-1 dry weight; capsaicin/control: 65.8 +/- 11.9 ng EB mg-1 dry weight; capsaicin/DTH: 84.3 +/- 7.6 ng EB mg-1 dry weight. 4. The tachykinins, substance P and neurokinin A (1.5 to 50 x 10(-11) mol per mouse, i.v.), induced an increase in vascular leakage in the small intestine of naive mice. The specific NK1 receptor antagonist, RP67580 (10(-9) mol per mouse, i.v.) was the most effective in reducing the substance P-induced plasma extravasation when compared with other NK receptor antagonists, FK224 and FK888. 5. Treatment of DNFB-sensitized mice with RP67580 (10-9 mol per mouse, i.v.) immediately before and 1 h after the DNBS challenge resulted in a significant reduction of the DTH-induced increase in vascular permeability at 24 h (vehicle/control: 107.5 +/- 8.8 ng EB mg-1 dry weight; RP67580/control:95.4 +/- 5.4 ng EB mg-1 dry weight; vehicle/DTH: 206.6 +/- 22.6 ng EB mg-1 dry weight; RP67580/DTH:132.6 +/- 13.6 ng EB mg-1 dry weight, P<0.05, ANOVA).6. These results suggest that sensory nerves are involved in the development of small intestinal DTH reactions in the mouse. NK1 receptors could play an important role in the initiation of the DTH-induced changes in vascular leakage.
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PMID:Delayed-type hypersensitivity-induced increase in vascular permeability in the mouse small intestine: inhibition by depletion of sensory neuropeptides and NK1 receptor blockade. 760 52

Inflammatory cell infiltrates and cell adhesion molecule expression have been examined in normal human skin after intradermal injection of sensory neuropeptides substance P (n = 6), vasoactive intestinal polypeptide (n = 6), and calcitonin gene-related peptide (n = 6) together with PBS as control (n = 4). Each neuropeptide induced rapid, time-dependent neutrophil influx into dermis, which was initially observed at 15 min and persisted for 8 h after injection. Increases in numbers of neutrophils with time after substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide were highly significant when compared with controls p < 0.005, p < 0.005, p < 0.005, respectively (analysis of variance). Substance P additionally induced marked eosinophilic accumulation at 4 and 8 h in four of six subjects. These changes paralleled rapid translocation of P-selectin from cytoplasmic Weibel-Palade granules to luminal membranes by 15 min, and significant up-regulation of E-selectin expression at 4 and 8 h. Increases in percentage of E-selectin positive vessels with respect to time after each neuropeptide were highly significant when compared with controls, p < 0.005, p < 0.005, p < 0.005 (ANOVA), respectively, and were significantly correlated with neutrophil infiltrates, r = 0.55, p < 0.001. VCAM-1 was not expressed, and constitutive ICAM-1 expression on dermal endothelium was unchanged at all time points examined (0-8 h). Induction of endothelial adhesion molecule expression by neuropeptides provides a mechanism for neutrophil accumulation in neurogenic inflammation. Substance P-induced eosinophil accumulation in the absence of VCAM-1 expression suggests that mechanisms distinct from VCAM-1/very late antigen-4 binding mediate selective tissue eosinophilia.
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PMID:Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin. 769 Aug

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.
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PMID:Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs. 839 88

We studied the local role of C-fibers, in the absence of systemic effects and blood components of inflammation, on lung responses to ozone. Guinea pigs were pretreated with capsaicin to deplete C-fibers or with vehicle. One week later their isolated, buffer-perfused lungs were exposed to 0.8 ppm ozone or air for 2 hr. In some lungs (9 or 10 each group), increasing doses of methacholine followed by capsaicin were injected into the pulmonary artery. In separate lungs (n = 5, each group), lung Substance P content by EIA and NK1 receptor characteristics by radioligand binding were measured. Analyses were performed by two-way ANOVA with a significant interaction indicative of C-fibers playing a role in ozone responses. Ozone increased R(L) and decreased C(dyn), effects which were apparently not dependent on C-fibers. Ozone increased responsiveness to methacholine, an effect which was reduced by depletion of C-fibers. Ozone increased and C-fiber depletion decreased lung responses to capsaicin. C-fiber depletion but not ozone decreased lung substance P content. C-fiber depletion increased the affinity but did not change the number of NK1 receptors, while ozone had no effect. We conclude that the ozone, in the absence of systemic effects and the blood components of inflammation, increased muscarinic reactivity in part via the local effects of C-fibers.
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PMID:The local C-fiber contribution to ozone-induced effects on the isolated guinea pig lung. 897 82

Controversy exists as to whether serotonin (5-HT) plays a neuroprotective role during brain injury. We sought to determine if prior 5-HT depletion alters gene expression patterns normally associated with NMDA receptor-mediated excitotoxicity of the rodent striatum. Adult male Sprague-Dawley rats were treated systemically with saline or p-chlorophenylalanine (pCPA, 350 mg/kg) to block 5-HT synthesis. After 3 days, these rats received unilateral injection (1 microliter) of quinolinic acid (QA, 40 micrograms in 0.1 M phosphate buffered saline, pH 7.4) or saline vehicle directly into the anterior striatum. All rats were sacrificed 6 or 48 h later. Striatal tissues containing the saline or QA injection site were subjected to Northern analysis of preprotachykinin (PPT), preproenkephalin (PPE), and zif/268 mRNAs, as well as HPLC-EC detection of monoamines. At the time of the intrastriatal injection, 5-HT levels were depleted greater than 95% by pCPA as compared to saline controls. At 48 h post-QA injection, PPT and PPE mRNAs were markedly reduced within the striatal lesion site of saline/QA and pCPA/QA groups with respect to their contralateral uninjected control sides. In the pCPA/QA group, striatal PPE and PPT mRNA levels were further reduced as compared to the saline/QA group with PPE mRNA reductions reaching statistical significance at 95% (ANOVA with Scheffe F-test). Exacerbation of the excitotoxic lesion in the 5-HT depleted rat was further exemplified by a larger increase in zif/268 mRNA measured at 6 h post-intrastriatal injection in the pCPA/QA group as compared to saline/QA animals (P < 0.05 by ANOVA with Scheffe F-test). These results suggest that 5-HT depletion may adversely affect neuronal survival following intrastriatal QA exposure and lend support to the hypothesis that increasing 5-HT levels during NMDA receptor-mediated excitotoxicity may spare neurons destined to degenerate.
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PMID:Serotonin depletion exacerbates changes in striatal gene expression following quinolinic acid injection. 901 51

1. In the Fisher 344 rat, tachykinins have been shown to cause the release of 5-hydroxytryptamine (5-HT) from airway mast cells, which then causes direct smooth muscle activation as well as the release of acetylcholine from cholinergic nerves. The aim of the present study was to examine the modulatory effects of 5-HT receptors on the neurokinin A (NKA)-induced release of endogenous 5-HT and airway smooth muscle contraction in the isolated Fisher 344 rat trachea. 2. The selective 5-HT2 receptor antagonist ketanserin (0.1 microM) produced an almost complete inhibition of the contractions caused by NKA (n=4, P<0.0001, two-way ANOVA), and a significant rightward shift of the concentration-response curve to 5-HT (n=8, P<0.001, two-way ANOVA). 3. The partial agonist for 5-HT1A receptors, 8-OH-DPAT (1 microM), and the full agonist for 5-HT1 receptors, 5-CT (0.3 microM), potentiated the submaximal contractions induced by the 5-HT2 receptor agonist alpha-methyl-5-HT (0.1 microM) (n=4; P<0.005 and P<0.05, respectively). 8-OH-DPAT (1 microM), as well as the 5-HT1A receptor antagonists pMPPI, SDZ 216525 and NAN-190 (0.1 microM each), caused significant inhibition of the tracheal contractions induced both by NKA (10 nM-3 microM) and 5-HT (10 nM-10 microM) (n=4-10). This suggests that activation of 5-HT1A receptors potentiates the 5-HT2 receptor-mediated contractions. 4. SDZ 216525 (0.1 microM) significantly reduced the maximal contraction produced by 1 microM NKA (n=10, P< 0.001), without affecting the release of endogenous 5-HT. These data rule out the involvement of a 5-HT1A receptor-mediated positive feedback mechanism of the 5-HT release from mast cells. 5. Even in the presence of atropine (1 microM), 8-OH-DPAT (1 microM) further reduced the maximal NKA-induced contraction (n=4, P<0.0001), while the contractions of the rat isolated trachea induced by electrical field stimulation and the concentration-response curve to carbachol were unaffected by pMPPI (0.1 microM), SDZ 216525 (0.1 microM), NAN-190 (0.1 microM) and 8-OH-DPAT (1 microM) (n=4-6). These data demonstrate that the 5-HT1A receptor-mediated potentiation of contractile responses is not due to nonspecific inhibition of airway smooth muscle contraction or to modulation of postganglionic nerve activation. 6. The selective 5-HT1B/1D receptor antagonist GR 127935, the selective 5-HT3 receptor antagonist tropisetron and the selective 5-HT4 receptor antagonists SB 204070 and GR 113808 (0.1 microM each) had no effect on the concentration-response curve for NKA (n=6-10), ruling out the involvement of 5-HT1B/1D, 5-HT3 and 5-HT4 receptors. 7. The alpha-adrenoreceptor antagonist phentolamine (1 microM) had no effect on the 5-HT-induced contractions (n=4), ruling out the involvement of alpha-adrenoreceptors. 8. In conclusion, the tachykinin-induced contraction of the F334 rat isolated trachea is mediated by the stimulation of 5-HT2 receptors. Activation of 5-HT1A receptors located on airway smooth muscle potentiates the direct contractile effects of 5-HT2 receptor activation. The 5-HT1B/1D, 5-HT3 and 5-HT4 receptors are not involved in the NKA-induced contraction of rat airways.
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PMID:Modulation by 5-HT1A receptors of the 5-HT2 receptor-mediated tachykinin-induced contraction of the rat trachea in vitro. 960 63

Tachykinin NK1 receptors are present on human pulmonary arteries. Addition of the specific tachykinin NK1 receptor agonist, [Met-OMe11]substance P produced a concentration-dependent relaxation (0.1 nM to 100 nM) in pulmonary arteries preconstricted with phenylephrine (30 microM). The EC50 (agonist concentration needed to produce 50% of the maximal relaxation) value for [Met-OMe11]substance P was 3.7+/-0.7 nM. The relaxation induced by [Met-OMe11]substance P was selectively inhibited by the tachykinin NK1 receptor antagonist CP 99994 (1 nM), with a pKb of 9.9+/-0.3. Treatment with the tachykinin NK2 receptor antagonist SR 48968 (100 nM) did not significantly affect the vasorelaxation due to [Met-OMe11]substance P (P > 0.05, one-way analysis of variance; ANOVA).
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PMID:Tachykinin NK1 receptor-mediated vasorelaxation in human pulmonary arteries. 968 25

1. This study investigates the role of tachykinins in a repeated challenge with dinitrobenzene sulphonic acid (DNS) on the tracheal vascular permeability in dinitrofluorobenzene (DNFB)-sensitized mice. 2. DNFB-contact sensitization was followed by an intranasal (i.n.) challenge with DNS. A second challenge with DNS was administered 24 h after the first challenge. To assess changes in tracheal vascular permeability, Evans blue dye accumulation in tracheal tissue was measured. 3. A repeated challenge with DNS in DNFB-sensitized mice led to a 2.8 fold increase in tracheal vascular permeability when compared to DNFB-sensitized and vehicle-challenged mice or a 2.5 fold increase when compared to DNFB-sensitized single DNS-challenged mice (P<0.001, ANOVA). 4. RP67580 (10-9 mol mouse-1 i.v.) reduced the increased tracheal vascular permeability induced by a second exposure to DNS in DNFB-sensitized mice completely when injected 15 min before the second challenge (P<0.001, ANOVA). 5. The increased tracheal vascular permeability response induced by the second exposure to DNS could be mimicked with i.n. application of capsaicin (10-10 mol mouse-1) or substance P (SP) (10-12 mol mouse-1) to DNFB-sensitized and single DNS-challenged mice. 6. These results suggest that both tachykinin NK1 receptors and sensory nerves are involved in the development of vascular hyperpermeability changes found in the trachea of DNFB-sensitized mice after a repeated DNS-challenge.
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PMID:Repeated challenge with dinitrobenzene sulphonic acid in dinitrofluorobenzene-sensitized mice results in vascular hyperpermeability in the trachea: a role for tachykinins. 1045 13


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