UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Media conditioned by compound 48/80-stimulated rat mast cells generated immunoreactive histamine-releasing peptide (HRP) when incubated at physiological pH with bovine serum albumin and the carboxypeptidase inhibitor, O-phenanthroline. The generation of immunoreactive HRP (IR-HRP) was time (after 3 h the concentration of IR-HRP was 20 nM), temperature, and pH dependent and was prevented by omitting albumin, by using media conditioned by nonstimulated mast cells, or by pretreatment of mast cells with disodium cromoglycate, an inhibitor of mast cell secretion. The amount of IR-HRP generated increased linearly with the number of mast cells stimulated and varied directly with the concentration of conditioned media. After removal of the media from stimulated mast cells, the remaining cell pellet retained its ability to generate IR-HRP for up to 8 h. Stimulation of mast cells by either neurotensin or substance P, or of sensitized cells by anti-IgE serum, also produced conditioned media that generated IR-HRP. The amount of IR-HRP formed by various conditioned media or by stimulated cell pellets was dependent upon the concentration of O-phenanthroline used. Including the chymase inhibitor, chymostatin, prevented the formation of IR-HRP in a dose-dependent manner. HPLC analysis showed four peaks of IR-HRP. The major one coeluted with synthetic HRP. These results indicate that the peptide, HRP, can be generated by stimulated mast cells incubated in the presence of albumin. They suggest that a chymase-like enzyme secreted by the mast cell is able to cleave albumin to yield HRP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulated rat mast cells generate histamine-releasing peptide from albumin. 768 97

Trigeminal sensory nerves contain and release the neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) in nasal mucosa. The effects of SP and CGRP on nasal secretion were tested in an in vivo model of guinea pig nasal mucosal secretion by topically applying the peptides directly to turbinates, and then lavaging the nostrils 10 min later. Concentrations of total protein, albumin, and 125I-bovine serum albumin (25I-BSA, injected intravenously at time 0 of the studies) were measured in lavage fluid. SP (beginning at 10(-8) M) and CGRP (beginning at 10(-6) M) stimulated the secretion of 125I-BSA indicating stimulation of plasma protein exudation. SP and CGRP increased total protein concentration at 10(-6) M indicating stimulation of glandular secretion. Topically applied thiorphan (1 microgram), an inhibitor of neutral endopeptidase, did not potentiate the maximal response to SP. However, thiorphan significantly prolonged the duration of 125I-BSA, total protein, and albumin secretion in response to SP indicating that the vascular and glandular responses were enhanced. This implies the presence of neutral endopeptidase, and demonstrates a regulatory role for this enzyme in vivo. These findings are consistent with the concept that SP and CGRP released by nociceptive sensory nerve axon responses in guinea pig nasal mucosa lead to plasma extravasation, albumin exudation, and glandular secretion, and that these mechanisms contribute to nasal responses to injury in this species.
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PMID:Effects of substance P and calcitonin gene related peptide (CGRP) on guinea pig nasal mucosal secretion in vivo. 769 Oct 22

Following incubation at 4 degrees C, [3H]-[Sar9,Met(O2)11]-substance P bound to tissue culture plates in a manner displaceable by substance P (SP). The IC50 for SP was about 100 nM. Although the total binding to the wells could be reduced by increasing the assay bovine serum albumin concentration, by the presence of divalent ions and by gelatin-precoating of the wells, the remaining binding could be inhibited by about 70% by SP, and would thus appear as "specific" binding in assays. The non-peptide antagonist (+/-)CP-96345 also inhibited the binding to the wells at high concentrations (IC50 about 2 mcM), whereas physalaemin did not. Physalaemin is thus a better agent to define non-specific binding. The consequences of the "specific" binding to the culture wells observed with SP to define non-specific binding are demonstrated in two cell systems: in cultured human umbilical vein endothelial cells, an apparent receptor density of about 100,000/cell is shown to be due mainly to binding to the wells, rather than the cells. In UC11MG cells, which express 40,000-60,000 NK-1 recognition sites/cell, the use of SP to define binding gives artifactually high KD and Bmax values, and an artifactually low potency (and Hill slope) of (+/-)CP-96345 when compared with data obtained using physalaemin to define the non-specific binding.
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PMID:"Specific" binding of [3H]-[Sar9,Met(O2)11]-substance P to tissue culture plates is found when substance P is used to define non-specific binding. 769 18

1. Synthetic amyloid beta-peptide was toxic to NB41A3 neuroblastoma cells in serum-free culture as judged by decreasing cell numbers and release of the cytosolic enzyme, lactic dehydrogenase. 2. Without amyloid beta-peptide, bovine serum albumin increased the number of cells surviving in culture. 3. In the presence of amyloid beta-peptide, BSA appeared to potentiate the amyloid beta-peptide toxicity. 4. The toxic dose response for amyloid beta-peptide varied between different cell lines (NB41A3, NB2a and IMR32), in a range of 100-1000 nM amyloid beta-peptide. 5. Amyloid beta-peptide toxicity was inhibited by the concurrent treatment of the cells with the tachykinin physalaemin with an ED50 of 10(-6) M.
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PMID:Comparative toxicity of amyloid beta-peptide in neuroblastoma cell lines: effects of albumin and physalaemin. 790 10

1. The GABA transaminase inhibitor and activator of glutamic acid decarboxylase, valproic acid is being used for the treatment of migraine. Its mechanism of action is unknown. We tested the effects of sodium valproate and GABAA-agonist muscimol on dural plasma protein ([125I]-bovine serum albumin) extravasation evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min) or substance P (SP) administration (1 nmol kg-1,i.v.) in anaesthetized Sprague-Dawley rats. 2. Intraperitoneal (i.p.) injection of sodium valproate or muscimol, but not baclofen (< or = 10 mg kg-1, i.p.) dose-dependently reduced dural plasma protein extravasation caused either by electrical trigeminal stimulation (ED50: 6.6 +/- 1.4 mg kg-1, i.p., and 58 +/- 18 micrograms kg-1, i.p. for valproate or muscimol, respectively) or by intravenous substance P administration (ED50: 3.2 +/- 1.4 mg kg-1, i.p. and 385 +/- 190 micrograms kg-1, i.p. for valproate or muscimol, respectively). 3. Valproate (6.6 mg kg-1, i.p.) or muscimol (58 micrograms kg-1, i.p.) had no effect on mean arterial blood pressure or heart rate when measured for 30 min after i.p. administration. 4. The GABAA-antagonist bicuculline (0.01 mg kg-1, i.p.) completely reversed the effect of valproate and muscimol on plasma extravasation following electrical stimulation or substance P administration, whereas the GABAB-receptor antagonist, phaclofen (0.01-1 mg kg-1, i.p.) did not. Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration. 5. Valproate decreased plasma extravasation following substance P administration in adult animals, neonatally treated with capsaicin by a bicuculline-reversible mechanism. This suggests that GABAA receptors are not found primarily on those afferent neurones or fibres which are sensitive to capsaicin treatment in neonatal rats.6. We conclude that sodium valproate blocks plasma extravasation in the meninges through GABAA mediated postjunctional receptors probably within the meninges. The dosages required are comparable to those used clinically. Agonists and modulators at the GABAA receptor may become useful for the development of selective therapeutic agents for migraine and cluster headache.
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PMID:Peripheral GABAA receptor-mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation. 856 34

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
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PMID:Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. 863 27

1. The possibility that tachykinin NK1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema formation induced by the i.d. injection of test agents was measured by the extravascular accumulation of intravenously (i.v.) injected 125I-labelled human serum albumin over a 30 min period. 3. The tachykinin NK1 agonist, GR73632 (30 pmol per site), induced local oedema formation which was potentiated by co-injection with the neuropeptide vasodilator, calcitonin gene-related peptide (CGRP, 10 pmol per site). The non-peptide tachykinin NK1 receptor antagonist, SR140333 (0.03-1 nmol per site co-injected, i.d.) significantly inhibited (0.3 nmol per site, P < 0.05; 1 nmol per site, P < 0.001) local oedema formation induced by GR73632 with CGRP but not that induced by histamine (10 nmol per site) with CGRP. 4. PNV (0.03-0.3 microgram per site) injected i.d. induced dose-dependent local oedema formation. SR140333 (1 nmol per site, co-injected i.d.) inhibited oedema formation; with complete inhibition observed at doses of 0.03 microgram (P < 0.05) and 0.1 microgram (P < 0.001); and partial inhibition (50%) observed with the highest dose of PNV, 0.3 microgram (P < 0.05). 5. Local oedema formation induced by PNV was not affected by systemic pretreatment with the bradykinin B2 receptor antagonist, Hoe 140 (80 nmol kg-1, i.v.), which was used at a dose which significantly inhibited oedema formation by bradykinin (1 nmol per site). 6. Local oedema formation induced by PNV was significantly inhibited (P < 0.01) by co-injection of the histamine H1 receptor antagonist, mepyramine (2.5 nmol per site), together with the 5-hydroxytryptamine (5-HT) antagonist, methysergide (2.8 nmol per site). 7. In the presence of all three antagonists (mepyramine 2.5 nmol per site; methysergide, 2.8 nmol per site and SR140333 1 nmol per site), the plasma extravasation induced by PNV was further significantly inhibited (P < 0.001, when compared with PNV injected i.d. alone; P < 0.05 when compared with PNV co-injected with mepyramine and methysergide and P < 0.01, when compared with PNV co-injected with SR140333). 8. These results suggest that oedema formation evoked by i.d. PNV in rat skin may be partially mediated via a mechanism involving tachykinin NK1 receptors and that this effect is independent of histamine and 5-HT.
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PMID:The effect of a tachykinin NK1 receptor antagonist, SR140333, on oedema formation induced in rat skin by venom from the Phoneutria nigriventer spider. 873 30

1. The effects of neuropeptide Y (NPY) receptor agonists (administered intravenously) were examined on plasma protein ([125I]-bovine serum albumin) leakage within dura mater evoked by unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min), capsaicin (1 mumol kg-1, i.v.) or substance P (1 nmol kg-1, i.v.) in anaesthetized Sprague-Dawley rats. 2. NPY (EC50: 5.6 nmol kg-1) and NPY fragment 13-36 [NPY (13-36)] (ED50: 4.3 nmol kg-1), an NPY Y2 receptor agonist, dose-dependently attenuated [125I]-bovine serum albumin extravasation from meningeal vessels when administered 10 min prior to electrical stimulation. [Leu31, Pro34]-NPY, an NPY Y1 and Y3 receptor agonist, inhibited the response at a higher dose only (23 nmol kg-1) (P < 0.05). 3. NPY also significantly decreased plasma protein extravasation induced by capsaicin (1 mumol kg-1) but not by substance P (1 nmol kg-1). 4. Pertussis toxin (20 micrograms kg-1, administered intracisternally 48 h prior to stimulation) blocked completely the inhibitory effect of NPY and NPY (13-36) but did not inhibit extravasation alone. 5. We conclude that NPY inhibits neurogenically-mediated plasma protein extravasation acting through presynaptic pertussis toxin-sensitive NPY Y2 receptors, possibly by inhibition of neuropeptide release from perivascular trigeminovascular afferents.
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PMID:Neuropeptide Y Y2 receptor-mediated attenuation of neurogenic plasma extravasation acting through pertussis toxin-sensitive mechanisms. 888 2

In this study, the severity and time course of inflammation induced by 4 organic solvents (acetone, cyclohexane, toluene and m-xylene), and the effect of neuropeptides during the inflammation were investigated in the hairless rat abdominal skin. Plasma extravasation used as a parameter of inflammation was measured by Evans blue and 125I-bovine serum albumin (BSA). Total volume of plasma extravasation induced by 4 organic solvents in 240-min exposure was as follows: toluene > m-xylene > cyclohexane > acetone = 0. While hydrophobic solvents (toluene, m-xylene, cyclohexane) induced plasma extravasation, the hydrophilic solvent, acetone, did not induce plasma extravasation. It was suggested that the severity and time course of plasma extravasation depend on chemical characteristics of the organic solvents. In immunohistochemical study, substance P (SP)-immunoreactive nerve fibers (IRNF) and calcitonin gene-related peptide (CGRP)-IRNF were intact during 240-min exposure to acetone. In contrast, cyclohexane, toluene, and m-xylene reduced the number of SP-IRNF and CGRP-IRNF in 10 min exposure and further reduced immunoreactivity. In hairless rats treated with systemic capsaicin, the above plasma extravasation was significantly reduced, along with SP-IRNF and CGRP-IRNF; however, protein gene product 9.5 (PGP 9.5)-IRNF was nearly intact. These results indicated that certain organic solvents induce instance of inflammation that vary widely in terms of their severity and time course, and that these differences are correlated with neuropeptides.
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PMID:Evaluation of organic solvent-induced inflammation modulated by neuropeptides in the abdominal skin of hairless rats. 947 57

Methodology was developed that uses reverse phase, high performance liquid chromatography (HPLC) to identify and quantify bradykinin, substance P, and neurokinin A contained in dental pulp tissue. Pulp tissue was prepared and homogenized from teeth frozen in liquid nitrogen, Known amounts of three substances found in inflamed tissue were added to the homogenized tissue and also to bovine serum albumin (BSA) (positive control), and supernatants were analyzed using HPLC. Other pulp tissue was prepared and analyzed without the addition of the substances. Recovery from the pulp and BSA with added substances was similar, with bradykinin recovered maximally. In pulp tissue without additions, all three substances were recovered. Thus HPLC appears to be a viable alternative to other methods for identification of these substances and allows for their quantification.
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PMID:Identification of bradykinin, substance P, and neurokinin A in human dental pulp. 959 64

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