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)

The role of substance P (SP) in allergic reactions of the skin was investigated. Spantide, a competitive inhibitor of SP, was injected intracutaneously into the volar aspect of the forearm prior to the following challenges: benzalkonium chloride (irritant delayed reaction), tuberculin (immunological delayed reaction), UVB irradiation, benzoic acid (non-immunological contact urticaria), different food allergens and latex (in patients with immunological contact urticaria). Only the immunological reactions of contact urticaria and the reaction to tuberculin were suppressed by the SP antagonist, indicating that SP is involved in their pathogenesis.
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PMID:Substance P antagonist inhibits immediate and delayed type cutaneous hypersensitivity reactions. 172 11

The effects of several protein modifying reagents, including phenoxybenzamine, N-ethylmaleimide (NEM), 5,5'-dithiobis (2-nitro)--benzoic acid (DTNB), p-chloromercuryphenyl sulfonic acid (PCMP) and p-bromophenacylbromide (PBPB), on the binding of 125I-Bolton Hunter substance P (125I-BHSP), 125I-Bolton Hunter eledoisin (125I-BHELE) and 3H-neurokinin B (3H-NKB)4 to cortical synaptosomes were examined. PCMP (10(-4) M), DTNB (10(-4) M) and NEM (10(-3) M) were without effect on the 125I-BHSP binding but reduced markedly the specific binding of 125I-BHELE or 3H-NKB. Although phenoxybenzamine and PBPB inhibited the 125I-BHSP binding when used in high concentrations (10(-4) M and 10(-3) M), they were more potent in inhibiting the 125I-BHELE or 3H-NKB binding. These results indicate that the NKB binding site is more sensitive to alkylating reagents than the SP binding sites and that these reagents can be used to distinguish SP and NKB receptors in the brain.
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PMID:Sulfhydryl reagents have different effects on substance P and neurokinin B binding sites on cortical synaptosomes in the rat. 243 90

We report the bioactivities of three biotinylated analogues of Substance P, [alpha-biotinyl-Lys3]Substance P-(3-11), [alpha-biotinyl-Arg1]Substance P, [epsilon-biotinyl-Lys3]Substance P, as well as the bioactivities of their complexes with avidin on guinea pig ileum. The rate of dissociation of an [alpha-biotinyl-Arg1]Substance P-avidin complex has been determined in the presence of 2-(4'-hydroxyazobenzene) benzoic acid and [3H]biotin. The biphasic dissociation of a 4:4 complex between [alpha-biotinyl-Arg1]Substance P and avidin led us to postulate the existence of two sets of binding sites, with the following rates of dissociation, at 4 degrees C, kappa-1 = 6 x 10(-4) x s-1 and kappa-1 = 1.2 x 10(-5) x s-1. We have confirmed this non-equivalence of the four binding sites of avidin by nuclear magnetic resonance using a spin-echo technique. The [alpha-biotinyl-Arg1]Substance P-avidin may be used for the affinity chromatography of Substance P receptors and the decreased affinity of this complex may be taken as an advantage since it can be displaced under mild conditions, i.e. by biotin-containing buffer.
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PMID:Avidin binding of biotinylated analogues of substance P. 619 48

The nervous and immune systems may communicate through the action of neurotransmitters on mast cells. We used patchclamp electrophysiology to assess the responses of rat peritoneal mast cells (PMC) to low levels of substance P (SP), which are likely to occur in situ. SP at 50 nM, or even 10,000 times reduced to 5 pM, triggered an outwardly rectified Cl- current (50 nM: 10 of 10 cells; 5 pM: 10 of 11 cells), although degranulation never occurred. Electrical responses were delayed (mean 102.6 s for 5 pM SP), appearing as brief current pulses. Reapplication of SP resulted in peak current augmentation (mean 15.3 pA before exposure to SP, 47.3 pA after 1st exposure, and 116.0 pA after 2nd exposure to 5 pM SP). Cells repetitively exposed to SP degranulated 5-15 min and > 25 min after the second exposure to 50 nM SP (10 of 10 cells) or 5 pM SP (5 of 9 cells), respectively. This effect was reduced by 10 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or when extracellular Ca2+ was removed, indicating a dependence on Cl- conductance and extracellular Ca2+. We propose that whole cell current oscillations in the absence of degranulation are the functional correlate of priming, a process that increases cellular responsiveness for the subsequent stimulation.
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PMID:Picomolar doses of substance P trigger electrical responses in mast cells without degranulation. 751 94

We previously demonstrated that the bradykinin-induced contraction of human isolated small bronchi is inhibited by indomethacin, capsaicin (N-methyl-N-6-nonenamide) and ruthenium red but not by tachykinin receptor antagonists. The thromboxane A2 receptor (TP receptor) antagonist GR32191 ((1R-(1 alpha(Z),2 beta,3 beta,5 alpha))-(+)-7-(5-(((1,1'-biphenyl)-4-yl)- methoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl)-4-heptenoic acid, hydrochloride) (10(-10) to 10(-8) M) dose dependently inhibited the effect of bradykinin, suggesting the mediation of the TP receptor in the action of bradykinin. With higher concentrations of GR32191 (10(-7) and 10(-6) M) bradykinin induced a relaxation which was inhibited by indomethacin and by the bradykinin B2 receptor antagonist Hoe 140 (D-Arg0[Hyp3,Thi-5,D-Tic7,Oic8]bradykinin). The thromboxane A2 synthase inhibitor dazoxiben (4-(-2-(1H-imidazol-1-yl)ethoxy) benzoic acid hydrochloride) 10(-6) M inhibited the bradykinin-induced contraction, suggesting that thromboxane A2 was involved in TP receptor stimulation. The thromboxane A2 mimetic U-46619 (9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-prostaglandin F2 alpha)-induced contraction of human distal bronchi was not inhibited by capsaicin and ruthenium red. Our data suggest that bradykinin contracts human isolated small bronchi through thromboxane A2 release. The inhibitory effect of ruthenium red and capsaicin on the bradykinin response may be due to inhibition of thromboxane A2 release or arachidonic mobilisation.
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PMID:Role of thromboxane A2 in bradykinin-induced human isolated small bronchi contraction. 754 24

Autonomic dysreflexia (AD) is a clinical phenomenon that affects patients with spinal cord injury (SCI) above the major sympathetic outflow tract. The lesion is most often at or above the T-6 level. Any noxious stimuli below this level initiate reflex sympathetic activity resulting in life threatening hypertension uncontrollable by the feedback parasympathetic activity. The episodes of hypertension generally persist until the offending stimulus is removed. Absence of higher control over reflex sympathetic activity due to transection of the cord is an anatomical explanation of the phenomenon. Current evidence suggests additional factors such as supersensitivity and possibly increased numbers of spinal alpha adrenoreceptors and peripheral microvascular adrenoreceptors as well as accumulation of substance P below the lesion. It has been suggested that substance P acts as a modulator, initiating the sympathetic event to produce a strong, slow and prolonged excitatory action. Autonomic dysreflexia is further accentuated by the absence of gamma amino benzoic acid (GABA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) below the lesion. GABA is an inhibitory neurotransmitter. It has been suggested that either NE or 5-HT may also act as an inhibitory neurotransmitter. Resetting of the baroreceptors at a lower level also plays an important role. The anatomical transection at or above T-6 then helps in maintaining and accentuating the biochemical changes that develop in patients with high spinal cord lesions. The current article reviews the pathophysiology and management of this potentially life threatening, yet easily treatable, phenomenon.
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PMID:Autonomic dysreflexia revisited. 764 Sep 77

1. We have examined the role of extracellular chloride in the mast cell secretion process. The immunologically-directed ligand, antibody to IgE (anti-IgE) required extracellular chloride ions for optimum secretion from rat peritoneal mast cells. In contrast, replacement of extracellular chloride did not alter the mast cell secretory response to compound 48/80, calcium ionophore A23187 or substance P. 2. Anti-IgE-stimulation of mast cells evoked a significant uptake of chloride ions compared to non-stimulated cells. The magnitude of chloride uptake correlated with the magnitude of stimulated histamine secretion. 3. Compound 48/80, substance P and A23187 did not alter the rate of chloride ion uptake, although these agents caused significant histamine secretion. 4. The Na+/K+/2Cl- cotransport inhibitor, furosemide, reduced the rate of anti-IgE-stimulated chloride uptake at a relatively high concentration (700 microM). However, the more potent Na+/K+/2Cl- cotransport inhibitors, bumetanide (100 microM) and piretanide (100 microM) had no effect on the stimulated chloride uptake. 5. Furosemide inhibited anti-IgE-induced histamine secretion, bumetanide potentiated the response and piretanide had no effect. This suggests that their respective action on histamine secretion are unrelated to inhibition of the Na+/K+/2Cl- carrier. 6. The chloride channel blocker, 5-nitro-2-((3-phenylpropyl)-amino)-benzoic acid (NPPB), reduced both anti-IgE-stimulated chloride uptake and the corresponding histamine secretion in a dose-dependent manner. The magnitude of the inhibitory action of the drug on these two cellular processes was comparable, implying that chloride channel activity is related to the mechanism of histamine secretion. 7. It is concluded that chloride uptake has a role in the control of Fc epsilon RI-mediated histamine secretion from rodent mast cells.
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PMID:Fc epsilon RI-mediated chloride uptake by rat mast cells: modulation by chloride transport inhibitors in relation to histamine secretion. 940 85

The present study was undertaken to identify and determine the mechanism of noncholinergic pathways for the induction of liquid secretion across airway epithelium. Excised porcine bronchi secreted substantial and significant quantities of liquid when exposed to acetylcholine, substance P, or forskolin but not to isoproterenol, norepinephrine, or phenylephrine. Bumetanide, an inhibitor of Na(+)-K(+)-2Cl(-) cotransport, reduced the liquid secretion response to substance P by 69%. Approximately two-thirds of bumetanide-insensitive liquid secretion was blocked by dimethylamiloride (DMA), a Na(+)/H(+) exchange inhibitor. Substance P responses were preserved in airways after surface epithelium removal, suggesting that secreted liquid originated from submucosal glands. The anion channel blockers diphenylamine-2-carboxylate (DPC) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) inhibited >90% of substance P-induced liquid secretion, whereas DIDS had no effect. DMA, DPC, and NPPB had greater inhibitory effects on net HCO(3)(-) secretion than on liquid secretion. Although preserved relative to liquid secretion, net HCO(3)(-) secretion was reduced by 39% in the presence of bumetanide. We conclude that substance P induces liquid secretion from bronchial submucosal glands of pigs through active transport of Cl(-) and HCO(3)(-). The pattern of responses to secretion agonists and antagonists suggests that the cystic fibrosis transmembrane conductance regulator mediates this process.
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PMID:Mechanism of substance P-induced liquid secretion across bronchial epithelium. 1150 91

Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, PGs, and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from beta cells, possibly through down-regulation of reactive oxygen species production. We hypothesized that UCP2 could also regulate mast cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2(-/-) mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and nonallergic triggers. Ucp2(-/-) BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic acid) porphyrin manganese(III). Furthermore, Ucp2(-/-) BMMCs also had greater production of both IL-6 and PGD(2) as well as ERK phosphorylation, which is known to regulate PG synthesis. Intradermal administration of substance P, an activator of skin mast cells, and challenge with DNP-human serum albumin after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2(-/-) mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.
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PMID:Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. 1984 69

Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma.
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PMID:Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle. 2399 76


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