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)

Calmodulin present in rat parotid homogenates activated cyclic AMP phosphodiesterase activity by 8 to 10 fold. The activation was Ca2+-dependent and reversed by trifluoperazine. Half-maximal inhibition required 12 microM trifluoperazine. Incubation of parotid slices with up to 40 microM trifluoperazine had no effect on the basal rate of amylase and K+ release or on cellular ATP content. Isoproterenol stimulated glucose utilization and substance P stimulated amylase secretion were also unaffected by 40 microM trifluoperazine. 20 or 40 microM Trifluoperazine however inhibited amylase secretion induced by isoproterenol, dibutyryl cyclic AMP, carbamoylcholine or phenylephrine. The possible involvement of calmodulin in regulating enzyme secretion following stimulation of the parotid gland with the various types of agonists is discussed.
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PMID:Does calmodulin mediate stimulus-secretion coupling in the parotid gland? Studies using trifluoperazine. 620 27

Intracellular Ca2+ is a regulator of active intestinal Na and Cl transport. Most studies have been done with rabbit ileum. Increasing intracellular Ca2+ decreases active Na and Cl absorption and/or stimulates active Cl secretion; lowering intracellular Ca2+ stimulates Na and Cl absorption. Based on studies with microvillus membrane vesicles from rabbit ileum, a direct effect of Ca2+ and calmodulin on linked Na and Cl uptake is established. Intracellular Ca2+ and cAMP affect the same transport processes and act in a nonadditive manner. Intracellular Ca2+ does not act by changing intestinal cAMP or cGMP contents, and increasing cAMP mobilizes intracellular Ca2+. Whether this Ca2+ is involved in regulation of ion transport is not known. The aspects of Ca2+ handling identified as involved in regulation of active intestinal Na and Cl transport include entry of Ca2+ across the basolateral membrane, mobilization of Ca2+ from intracellular stores, and involvement of the Ca2+-binding protein calmodulin. Several neurohumoral substances alter intestinal transport by Ca2+-dependent mechanisms and appear to act primarily by increasing (serotonin, carbachol, substance P, and neurotensin) or decreasing (dopamine) Ca2+ entry across the basolateral membrane of intestinal epithelial cells.
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PMID:Ca2+ in the control of active intestinal Na and Cl transport: involvement in neurohumoral action. 630 16

Calmodulin (CaM) binding by turkey gizzard myosin light chain kinase (MLCK) causes subtle changes in the fluorescence emission and polarization excitation spectra of the enzyme. Fluorescence experiments using 9-anthroyl-choline (9AC), which competes with ATP in binding, demonstrate mutually stabilizing interactions between the CaM and ATP binding sites corresponding to delta G = -0.6 to -0.7 kcal/mol. Fluorescence titrations in the presence of 9AC or 5,5'-bis[8-(phenylamino)-1-naphthalenesulfonate] confirm the stoichiometry of 1 mol of CaM/MLCK. Phosphorylation of MLCK has no effect on either the protein fluorescence or the binding of ATP and 9AC. The dissociation constant for the MLCL-CaM complex is increased approximately 500-fold on phosphorylation. Values of Kd for the phosphorylated enzyme range from 0.5 to 1.1 microM in 0.2 N KCl, pH 7.3, 25 degrees C. We showed competition between MLCK and other CaM binding proteins and peptides by using both fluorescence and catalytic activity measurements. Competition for CaM occurs with ACTH, beta-endorphin, substance P, glucagon, poly(L-arginine), myelin basic protein, troponin I, and histone H2A. Phosphorylation of the last three proteins by the adenosine cyclic 3',5'-phosphate dependent protein kinase diminishes their ability to compete. Phosphorylation of MLCK by the protein kinase gives 0.95 +/- 0.04 and 2.2 +/- 0.4 mol of incorporated 32P in the presence and absence of CaM, respectively. These stoichiometries agree with those recently reported [Conti, M. A. & Adelstein, R. S. (1981) J. Biol. Chem. 256, 3178].
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PMID:Functional interactions between smooth muscle myosin light chain kinase and calmodulin. 689 95

The present study was aimed to determine the effect of calmodulin inhibitors on the relaxant response of isolated dog and monkey cerebral arteries to vasodilator nerve stimulation, which is hypothesized to be mediated by nitric oxide (NO) from nerve endings. The relaxations caused by nerve stimulation by electrical pulses in endothelium-denuded arteries were attenuated by treatment with calmidazolium and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride) and were abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, and tetrodotoxin. The calmodulin inhibitors also attenuated the relaxations caused by nicotine and substance P, which were endothelium-independent and -dependent, respectively, but did not influence the relaxant response to NO. It is concluded that calmodulin is required for activation of the NO synthase present in the vasodilator nerve as well as that in the endothelium.
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PMID:Inhibition by calmodulin antagonists of the neurogenic relaxation in cerebral arteries. 751 92

Smooth muscle cells isolated from the circular muscle layer of cat esophagus and lower esophageal sphincter (LES) exhibit distinct contractile intracellular signal transduction pathways in response to acetylcholine. To determine whether these contractile pathways are muscle type dependent, the authors examined the signal transduction pathways utilized by substance P and bombesin, which in other tissues, use different signal transduction pathways, and by the GTP analog, guanosine 5'-O-3-thiotriphosphate (GTP gamma S), which activates all available G proteins. Western blot analysis of esophageal and LES circular muscle revealed the presence of Gq-G11 (42 kD), Gi1-Gi2 (40 kD) and Go-Gi3 (40 kD) types of G proteins. The responses of esophageal cells to bombesin and substance P were blocked by 1) a Gi3 protein antibody, 2) the inhibitor of specific phosphatidylcholine-phospholipase C (PLC) D609 potassium tricyclo-[5.2.1.0(2.6)]-decyl-(9[8])-xanthogenate, 3) inhibition of phosphatidic acid phosphohydrolase by propranolol, 4) the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and 5) incubation in Ca(++)-free medium. Conversely, the responses of LES muscle cells to bombesin and substance P were blocked by 1) a Gq-G11 antibody, 2) a phosphatidylinositol-specific PLC antagonist U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione), 3) the calmodulin inhibitor CGS9343B (1,3-Dihydro-1-[1-((4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]benzoxazepin++ +-4 - yl)methyl-4-piperindinyl]-2H-benzimidazol-2-one maleate) and 4) incubation in Sr++. After permeabilization by saponin, inositol 1,4,5-trisphosphate contracted LES but not esophageal cells. The inositol 1,4,5-trisphosphate receptor antagonist heparin and depletion of intracellular Ca++ stores by thapsigargin or A23187 4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol- 2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-, [6s-[6.alpha. (2S*,3S*),8.beta. (R*), 9.beta., 11. alpha.]]-(9Cl), blocked bombesin- and substance P-induced contraction of LES but not of esophageal muscle. In addition, contraction in response to GTP gamma S, which activates all G proteins, was blocked in esophageal cells by a Gi3-protein antibody, propranolol, D609 and H7. In LES muscle cells, the response to GTP gamma S was blocked by a Gq protein antibody, U-73122 and CGS934B. These data demonstrate that, in esophageal muscle, different agonists activate the same Gi3 protein, phosphatidylcholine-specific phospholipases and protein kinase C-dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Agonist-independent, muscle-type-specific signal transduction pathways in cat esophageal and lower esophageal sphincter circular smooth muscle. 753 46

Substance P (SP) and lipopolysaccharide (LPS) stimulated interleukin-6 (IL-6) gene expression, as well as IL-6 protein secretion in the human astrocytoma cell line U373 MG. Staurosporine, an inhibitor of protein kinase C (PKC), entirely blocked SP- but not LPS-induced IL-6 release. In addition, the down regulation of PKC inhibited the SP response and only marginally altered LPS activation. Differently from SP, LPS-induced IL-6 release was markedly reduced by W7, a calmodulin antagonist. Moreover, SP interacted in a synergistic manner with LPS. Thus, neural (SP) and bacterial (LPS) mediators stimulate U373 MG IL-6 release via distinct, though not antagonistic, activation pathways.
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PMID:Interleukin-6 production by U373 MG, a human astrocytoma cell line: different pathways involved in substance P and lipopolysaccharide activation. 754 Oct 52

Solution x-ray scattering using synchrotron radiation as an x-ray source has been used to study the solution structure of calmodulin complexed with substance P, a undecapeptide neurotransmitter. The x-ray data indicate that the complex has a compact globular structure, the formation of which is dependent upon the binding of Ca2+ to calmodulin. In the Ca(2+)-saturated condition, the radius of gyration of complexed calmodulin was 4.2 A smaller than that of uncomplexed calmodulin. The Ca(2+)-dependent change in radius of gyration of calmodulin with substance P is complete by the third and fourth Ca2+ binding. The behavior of the Guinier plot at small-to-moderate angles for uncomplexed calmodulin corresponds to a dumbbell shape. The Guinier plot for complexed calmodulin, however, corresponds to a non-dumbbell shape. The susceptibility of calmodulin to proteolytic attack with trypsin was used to examine the nature of the calmodulin complexed with substance P. In the presence of equimolar substance P, the first and second Ca2+ binding to calmodulin was enough to form a trypsin-resistant complex. These biochemical and x-ray data suggest that the binding of substance P to calmodulin is completed when the C-terminal half of calmodulin is occupied by Ca2+, while a significant structural change of calmodulin in the complex is still induced by successive Ca2+ occupancy on the N-terminal half of this molecule.
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PMID:Calcium-dependent changes in structure of calmodulin with substance P. 768 32

The neuro-endocrine cells of fish skin and respiratory surfaces, and their bioactive secretion as far as is known, are reviewed, and compared with similar elements in tetrapods, particularly amphibians. In the skin of teleost fish, immunohistochemistry has shown that Merkel cells react for serotonin, neuron-specific enolase and enkephalins. The pharmacology is not established in dipnoans or lampreys. In some teleosts, neuromasts react for substance P and leu-enkephalins; substance P is also reported from some ampullary organs (electroreceptors). Taste buds of teleosts may react for enkephalin and substance P. Basal cells of taste buds react for serotonin and neuron-specific enolase. Some unicellular skin glands of teleosts express bioactive compounds, including serotonin and some peptides; this ectopic expression is paralleled in amphibian skin glands. The dipnoan Protopterus has innervated pulmonary neuro-endocrine cells in the pneumatic duct region with dense-cored vesicles. In Polypterus and Amia the lungs have serotonin-positive neuro-endocrine cells that are apparently not innervated. In fish gills, a closed type of neuro-endocrine cell reacts for serotonin, an open type for enkephalins and some calcium-binding proteins (calbindin, calmodulin and S-100 protein). The functions of neuro-endocrine cells in fishes await investigation, but it is assumed they are regulatory.
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PMID:Distribution patterns of the paraneuronal endocrine cells in the skin, gills and the airways of fishes as determined by immunohistochemical and histological methods. 798 86

In NG 108-15 clonal cells, extracellular application of micromolar concentrations of serotonin [5-hydroxytryptamine (5-HT)] and substance P induces the opening of a cation permeability monitored by the influx of [14C]-guanidinium. The serotoninergic component of this cation permeability is linked to 5-HT3 receptor activation, whereas the substance P component probably involves an "N-terminal-dependent substance P receptor." In this study, [14C]guanidinium influx triggered by 1 microM 5-HT plus 10 microM substance P was shown to be insensitive to tetrodotoxin, verapamil, diltiazem, nimodipine, and omega-conotoxin, as expected from a process independent of voltage-sensitive sodium and calcium channels. In contrast, [14C]guanidinium influx was inhibited by millimolar concentrations of extracellular calcium and by the chelation of intracellular calcium by bis-O-aminophenoxyethanetetraacetic acid. The inhibition by extracellular calcium apparently involved a competition between the divalent cation and [14C]guanidinium for the same channel. When NG 108-15 cells were exposed to X537A, an ionophore that specifically induces release of calcium from intracellular stores, [14C]guanidinium uptake was markedly increased even in the absence of 5-HT and/or substance P. Conversely, [14C]guanidinium influx due to the latter substances could be reversibly and dose-dependently blocked by various drugs that possess calmodulin-antagonizing properties. These results strongly suggest that the cation permeability opened by 5-HT and substance P in NG 108-15 cells involves a calcium/calmodulin-dependent process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological evidence for the involvement of calcium/calmodulin in serotonin 5-HT3 receptor-mediated cation permeability in NG 108-15 cells. 818 30

The role of platelet-activating factor (PAF) and substance P in stimulating abnormal motor activity during ileal inflammation was investigated in conscious dogs. All test substances were infused close-i.a. in short segments of the ileum. Ileal inflammation was induced by mucosal exposure to a series of ethanol and acetic acid infusions. In the normal state, PAF stimulated phasic contractions and some giant migrating contractions (GMCs), whereas substance P stimulated only phasic contractions. During inflammation, PAF stimulated a significantly greater number of GMCs, but there was no significant difference in the area under phasic contractions between the normal and inflamed states. Atropine, tetrodotoxin, hexamethonium, verapamil, diltiazem, and dantrolene significantly inhibited the response to PAF in both the normal and the inflamed state. By contrast, inhibition of nitric oxide by N omega-nitro-L-arginine methyl ester enhanced the contractile response to PAF. N-(6-ammohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride, a calmodulin antagonist, did not affect the response to PAF. Methacholine, neostigmine and motilin stimulated only phasic contractions during the normal state, but they stimulated both phasic contractions and GMCs during the inflamed state. We conclude that PAF is one of the inflammatory response mediators that may stimulate GMCs during ileal inflammation. The inflammatory response may modulate the enteric neuronal and cellular control of contractions such that the cholinergic mechanisms of stimulation of GMCs are sensitized during inflammation.
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PMID:Platelet-activating factor (PAF) stimulates giant migrating contractions during ileal inflammation. 885 95


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