UNIPROT:P20366 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

We studied whether substance P (SP) facilitates induction of long-term potentiation (LTP) in adult rat visual cortex slices, using intracellular recordings of postsynaptic potentials (PSPs) elicited by white matter stimulation. Tetanic stimulation in normal medium induces no change of the PSP amplitude. In SP-containing medium, by contrast, tetanization potentiated the PSP amplitude in 5 over 7 cells examined. Although the other 2 cells underwent no change, the overall effect of SP was an increase in the probability of LTP induction. This effect of SP was canceled out by bath-application of the non-peptide antagonist CP96,345 (n = 7) or intracellular application of guanosine 5'-beta-thio-diphosphate (GDP beta S; n = 7). These results suggest that SP increased LTP susceptibility of neurons in the adult rat visual cortex through SP receptor-mediated mechanisms.
...
PMID:Facilitatory effects of substance P on the susceptibility to long-term potentiation in the visual cortex of adult rats. 769 77

1. Sensitization of the contractile system in response to combinations of excitatory agonists acetylcholine (ACh), methacholine, histamine and neurokinin A (NKA) was investigated in colonic circular smooth muscle of dog, NKA (1 nM) potentiated the contractile response to 1 microM ACh, but did not increase the fura-2 fluorescence ratio (R340/380). Contraction in response to low concentrations of either methacholine or histamine was potentiated significantly by 0.1 microM 4-phorbol 12,13-dibutyrate (PDBu), suggesting that activation of protein kinase C can potentiate contraction at threshold concentrations of agonists. 2. Variability in the sensitivity of the contractile system to Ca2+ was demonstrated over a range of agonist concentrations. KCl, ACh, histamine and NKA each produced a concentration-dependent increase in the amplitude of phasic contractions and R340/380. However, ACh, histamine and NKA each induced maximal increases in R340/380 at concentrations less than that needed to induce maximum force. 3. In depolarized muscles, NKA (50 nM) and PDBu (1 microM) each increased the magnitude of tonic contraction with no change or a decrease in both R340/380 and myosin light chain phosphorylation. In alpha-toxin-permeabilized fibres, 0.1 microM PDBu and 1 microM NKA shifted the Ca(2+)-force response to the left. Ca(2+)-induced contractions were also potentiated by 100 microM GTP-gamma-S or 1 microM NKA plus 10 microM GTP. Potentiation of contraction by NKA and GTP was antagonized by 10 microM GDP-beta-S. 4. The results suggest that endogenous agonists acting via G-proteins sensitize the contractile element of colonic smooth muscle in part by activation of protein kinase C. In some cases, sensitization may be secondary to increased myosin phosphorylation (ACh), but in other cases it appears to be independent of increased myosin light chain phosphorylation (NKA and PDBu). Therefore regulatory mechanisms in addition to myosin phosphorylation contribute to the apparent sensitization of the contractile system to Ca2+.
...
PMID:Sensitization of the contractile system of canine colonic smooth muscle by agonists and phorbol ester. 770 35

1. Single smooth muscle cells were isolated from the longitudinal muscle layer of the guinea-pig ileum and within 10 h Ca(2+)-currents (ICa) were recorded using the whole-cell patch clamp technique. 2. Histamine (10 microMs) and bradykinin (BK, 1 microM) suppressed ICa; the effect had two phases: a rapid and transient suppression of ICa followed by a sustained suppression. Acetylcholine and substance P appeared to have similar effects but these were not investigated in detail. 3. The effects of histamine and BK on ICa were established by high intracellular concentrations of the Ca2+ buffer EGTA (30 mM) or 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (5 mM) in the absence of Ca2+ added to the pipette solution. When [Ca2+]i was strongly buffered to 125 or 190 nM by BAPTA-Ca2+ mixtures in the pipette the transient suppression of ICa was blocked but the sustained effect still occurred. This indicated that the transient effect was caused by a rise in [Ca2+]i. The sustained effect, in contrast, did not seem to be caused by a rise in [Ca2+]i but did show Ca2+ dependence because it did not occur if [Ca2+]i was abnormally low. 4. Application of caffeine (10 mM) to deplete stored Ca2+ or intracellular heparin (1 mM) to block the action of D-myo-inositol 1,4,5-trisphosphate (IP3) to release stored Ca2+ prevented the transient but not the sustained suppression of ICa. Heparin also blocked the transient Ca(2+)-activated K+ current in response to histamine or BK. Both transient and sustained suppressions of Ca2+ channel activity were observed in the absence of extracellular Ca2+ when current was carried mostly by Na+ ions. 5. Intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S; 10 or 100 microM) induced a gradual decline of ICa upon which transient decreases of current were superimposed. Histamine caused a larger than normal inhibition of ICa and no recovery occurred on wash-out. Intracellular guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S; 1 mM) abolished the effects of histamine and BK on ICa.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Inhibitory effects of histamine and bradykinin on calcium current in smooth muscle cells isolated from guinea-pig ileum. 824 98

The effects of tachykinins on primary afferent neurons of bullfrog dorsal root ganglia (DRG) were examined by using whole-cell patch-clamp methods. Neurokinin A (NKA) caused inward current (INKA) in a concentration-dependent manner. Concentration-response curve showed that the EC50 for NKA was 6 nM. The INKA showed strong tachyphylaxis, when NKA was continuously applied for more than 1 min. Substance P (SP) also produced inward current with potency similar to that of NKA. Neurokinin B (NKB) was less effective in producing the inward current. The order of agonist potency was NKA = SP >> NKB. Spantide ([D-Arg1, D-Trp7.9, Leu11]SP), a non-selective peptide antagonist at tachykinin receptors, reduced the tachykinin-induced current. CP-99,994, a selective non-peptide antagonist for neurokinin-1 (NK1) receptor, inhibited the inward currents produced by NKA and SP. The INKA was associated with decrease in K+ conductance. NKA suppressed both a voltage-dependent K+ current, the M-current (IM), and a voltage-independent background K+ current, IK(B). Intracellular dialysis with GTP gamma S (100 nM) or GDP beta S (100 microM) depressed the INKA. Pre-treatment of DRG neurons with pertussis toxin (PTX) did not prevent the INKA. Depletion of intracellular ATP depressed the INKA. These results suggest that the tachykinin-induced inward current is mediated through the NK1 receptor which mainly couples to PTX-insensitive G-protein in bullfrog primary afferent neurons.
...
PMID:Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons. 872 87

To investigate substance P (SP) receptors on an established human astrocytoma cell line (U-87 MG), [3H][Sar9,Met(O2)11]-SP, a selective SP receptor agonist, was used to identify and characterize the cell membrane binding sites for SP. SP receptor mRNA was examined by solution hybridization analysis, and the existence of SP binding protein on the surface of membranes was evaluated by flow cytometry using an anti-SP binding protein antibody. In U-87 MG and U-373 MG RNA preparations, transcripts were identified that corresponded to both mature and partially spliced receptor forms. In U-87 MG cell membrane-enriched preparations, the binding of [3H][Sar9,Met(O2)11]-SP was found to be time and cell number dependent, specific, saturable, and of high affinity. Equilibrium binding analysis revealed a single class of binding sites with an apparent KD of 1.15 +/- 0.15 nM and a Bmax of 108 +/- 9.8 fmol/mg of protein. [3H][Sar9, Met(O2)11]-SP binding was basically not influenced by addition of mono (Na+, Li+) or divalent (Mg2+, Mn2+, Ca2+) cations; only high doses of divalent cations decreased the binding. GTP and guanylyl-5'-imidodiphosphate, but not GDP and GMP, reduced the Bmax without changing the affinity of [3H][Sar9,Met(O2)11]-SP. We also examined the effects of pretreatment with three lectins [concanavalin A (con A), wheat germ agglutinin (WGA), and Lens culinaris agglutinin (LCA)] to determine the nature of carbohydrate chains on the U-87 MG cell. Of three lectins analyzed for effects on agonist binding, WGA and LCA had an inhibitory effect, whereas con A was ineffective. These results suggest that SP receptors on the human astrocytoma cell line U-87 MG have either a biantennary complex-type or a high mannose-type of carbohydrate chain and may be regulated by GTP-binding protein(s).
...
PMID:Human astrocytoma cells (U-87 MG) exhibit a specific substance P binding site with the characteristics of an NK-1 receptor. 886 85

We examined the intracellular mechanisms of substance P-induced superoxide anion (O2-) production in human neutrophils. Addition of substance P (30 microM) caused O2- production and biphasic increases in intracellular Ca2+ concentrations ([Ca2+]i) (early transient and subsequent sustained components) associated with the formation of inositol 1,4,5-trisphosphate (IP3). O2- and [Ca2+]i were assayed by using ferricytochrome C and fura 2-AM, respectively. These responses were abolished by tachykinin NK1 receptor antagonists, [D- Pro9[spiro-gamma-lactam],Leu10,Trp11]physalaemin-(1-11) (GR82334) or [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), and an intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). Inhibition of IP3 formation by GTP-binding protein (G-protein) inactivators such as guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and islet-activating protein (IAP), or a phospholipase C inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)- trien-17-yl]amino]hexyl]1 H-pyrrole-2,5-dione (U-73122), blocked the substance P-induced O2- production and biphasic increases in [Ca2+]i. An IP3 receptor antagonist, heparin, reduced both the substance P-induced O2- production and the transient increase in [Ca2+]i without any significant effects on the sustained increase in [Ca2+]i. Protein kinase C inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and calphostin C, only slightly suppressed O2- production, and abolished the sustained increase in [Ca2+]i without any significant effects on the transient increase in [Ca2+]i. A Ca2+ entry blocker, nicardipine, completely inhibited the sustained increase in [Ca2+]i without affecting O2- production and the transient increase in [Ca2+]i. These results suggest that the tachykinin NK1 receptor/G-protein-linked IP3 formation with the resulting IP3-induced transient increase in [Ca2+]i is the main signal transduction pathway for substance P-stimulated O2- production in neutrophils.
...
PMID:Intracellular signaling pathway of substance P-induced superoxide production in human neutrophils. 890 Oct 22

1. The effects of substance P (SP) and related tachykinins on the function of gamma-aminobutyric acid-A (GABAA) receptors were examined in acutely dissociated neurones of bullfrog dorsal root ganglia (DRG) by using whole-cell voltage-clamp techniques. 2. Application of SP (10 nM to 1 microM) depressed inward currents produced by GABAA receptor activation (IGABA). Neurokinin A (NKA) and neurokinin B (NKB) also depressed IGABA; the rank order of agonist potency was SP > NKA > NKB. Spantide ([D-Arg1, D-Trp7,9,Leu11]SP) and L-703,606, NK1 receptor antagonists, blocked the SP-induced depression of IGABA. 3. SP irreversibly depressed IGABA, when neurones were intracellularly dialysed with GTP gamma S. Intracellular application of GDP beta S prevented the SP-induced depression of IGABA. Pertussis toxin (PTX) did not block the inhibitory effect of SP on IGABA. 4. The depression of IGABA produced by SP was inhibited by H-7 and PKC(19-36), protein kinase C (PKC) inhibitors, but not by H-9 and HA-1004, protein kinase A inhibitors. IGABA was suppressed by application of sn-1,2-dioctanoyl glycerol (DOG), a PKC activator. 5. It is concluded that activation of neurokinin-1 (NK1) receptors downregulates the function of the GABAA receptor of primary sensory neurones through a PTX-insensitive G-protein. PKC may be involved in the transduction pathway of the tachykinin-induced inhibition of the GABAA receptor.
...
PMID:Substance P suppresses GABAA receptor function via protein kinase C in primary sensory neurones of bullfrogs. 891 Feb 28

We examined the intracellular mechanisms of substance P induced oxyradical production in rheumatoid synovial cells by the luminol-dependent chemiluminescence method. After stimulation with substance P (30 microM), single synovial A (macrophage-like) or B (fibroblast-like) cells released oxyradicals such as superoxide anions (O2-) and/or hypochlorous anions (OCl-) under a microscope equipped with an ultrasensitive photonic image intensifier. The substance P induced oxyradical production was blocked by a tachykinin NK1 (NK1) receptor antagonist, GR82334, GTP-binding protein (G-protein) inactivators, GDP beta S and islet-activating protein (IAP), and a phospholipase C (PLC) inhibitor, U-73122. Substance P (30 microM) also induced a transient increase in the intracellular Ca2+ concentration ([Ca2+]i) in both synovial A and B cells as measured by a Ca2+ indicator, fura 2, BAPTA-AM and an inositol-1,4-5-triphosphate (IP3) receptor antagonist, heparin, inhibited the substance P induced increase in [Ca2+]i, but they had no effects on oxyradical production. In contrast to the effects of BAPTA-AM and heparin, protein kinase C (PKC) inhibitors, H-7 and calphostin C, completely inhibited substance P induced oxyradical production without any significant effects on [Ca2+]i increase. These findings suggest that the NK1 receptor/PLC-linked diacylglycerol (DAG) formation with the resulting activation of PKC is the main signal transduction pathway for substance P stimulated oxyradical production in synovial cells.
...
PMID:Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells. 896 80

The selectivity in coupling of various receptors to GTP-binding regulatory proteins (G proteins) was examined directly by a novel assay entailing the use of proteins overexpressed in Spodoptera frugiperda (Sf9) cells. Activation of G proteins was monitored in membranes prepared from Sf9 cells co-expressing selected pairs of receptors and G proteins (i.e. alpha, beta1, and gamma2 subunits). Membranes were incubated with [35S]guanosine 5'-(3-O-thio)triphosphate (GTPgammaS) +/- an agonist, and the amount of radiolabel bound to the alpha subunit was quantitated following immunoprecipitation. When expressed without receptor (but with beta1gamma2), the G protein subunits alphaz, alpha12, and alpha13 did not bind appreciable levels of [35S]GTPgammaS, consistent with a minimal level of GDP/[35S]GTPgammaS exchange. In contrast, the subunits alphas and alphaq bound measurable levels of the nucleotide. Co-expression of the 5-hydroxytryptamine1A (5-HT1A) receptor promoted binding of [35S]GTPgammaS to alphaz but not to alpha12, alpha13, or alphas. Binding to alphaz was enhanced by inclusion of serotonin in the assay. Agonist activation of both thrombin and neurokinin-1 receptors promoted a modest increase in [35S]GTPgammaS binding to alphaz and more robust increases in binding to alphaq, alpha12, and alpha13. Binding of [35S]GTPgammaS to alphas was strongly enhanced only by the activated beta1-adrenergic receptor. Our data identify interactions of receptors and G proteins directly, without resort to measurements of effector activity, confirm the coupling of the 5-HT1A receptor to Gz and extend the list of receptors that interact with this unique G protein to the receptors for thrombin and substance P, imply constitutive activity for the 5-HT1A receptor, and demonstrate for the first time that the cloned receptors for thrombin and substance P activate G12 and G13.
...
PMID:Reconstitution of receptors and GTP-binding regulatory proteins (G proteins) in Sf9 cells. A direct evaluation of selectivity in receptor.G protein coupling. 899 27

Four tachykinin-related peptides, locustatachykinin 1-4 (LomTK 1-4) are distributed in interneurons throughout the central nervous system of the locust Locusta migratoria and may have important roles as neurotransmitters or neuromodulators. In search of the central actions of LomTKs, we analyzed the response of the efferent dorsal unpaired median (DUM) neurons in the locust metathoracic ganglion. Immunocytochemistry, using an antiserum against LomTK 1, combined with intracellular filling of efferent DUM neurons with Lucifer yellow, revealed that LomTK-immunoreactive fibers are in close proximity to dendritic arborizations of the DUM neurons. Hence, LomTKs may act on DUM neurons by releasing locally in the metathoracic ganglion. Intracellular recordings were made from somata of DUM neurons, and LomTKs were either bath-applied to an isolated metathoracic ganglion or pressure-ejected onto the DUM neuron soma. LomTK 1 at concentrations of 0.1 mM-0.1 microM caused a relatively slow, reversible depolarization with a subsequent increase in the frequency of action potential firing. Amino-terminally truncated forms of LomTK 1 were applied to DUM neurons. The heptapeptide [3-9]-LomTK 1 had a substantially reduced activity, and bioactivity was lost after further truncation. Spantide 1, an antagonist of mammalian tachykinin receptors, reversibly blocked the effect of LomTK 1. The effect of LomTK 1 was clearly reduced in the presence of GDP-beta-S, a stable analog of GDP that inactivates G-proteins. The action of LomTK 1 was potentiated by both IBMX and theophylline, two cyclic AMP (cAMP) phosphodiesterase inhibitors. The action of LomTK 1 was mimicked by pressure-ejecting 8-bromo-cAMP, a membrane permeable analog of cAMP, and by forskolin, an adenylate cyclase activator. Furthermore, cAMPS, a blocker of protein kinase A activity, reduced the effect of LomTK 1. These findings indicate that cAMP is involved in mediating DUM neuron depolarization.
...
PMID:Peptidergic activation of locust dorsal unpaired median neurons: depolarization induced by locustatachykinins may be mediated by cyclic AMP. 929 67

<< Previous 1 2 3 Next >>