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)

Substance P (SP) is an undecapeptide neuromediator that stimulates human T-lymphocyte function by binding to stereospecific membrane receptors. Human IM-9 cultured B-lymphoblasts express approximately 20,000 receptors per cell for [125I]SP with a Kd of 0.3 nM. [125I]SP was specifically crosslinked by disuccinimidyl suberate to IM-9 cell membrane proteins of 78, 58, and 33 kDa. An indirect immunoaffinity purification procedure has now been developed based on immunoabsorption of detergent-solubilized [125I]SP-labeled IM-9 cell membrane proteins to anti-SP antibody that was bound to an epoxide ultraffinity high-performance liquid chromatography column, followed by elution in acidic 8 M urea. The 58- and 33-kDa SP-receptor complexes were purified to apparent homogeneity by immunoaffinity chromatography and identified by autoradiography and silver staining of sodium dodecyl sulfate-polyacryl-amide gels.
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PMID:Immunoaffinity purification of membrane protein constituents of the IM-9 lymphoblast receptor for substance P. 282 37

Some factors influencing the oxidative activity of upper horizons of spruce forest soils (a mixture of fermentative and humus layers) toward intermediates of the oxidative part of the sulphur cycle were investigated. Preincubation of the soil with added cysteine, sulphide, elemental sulphur or thiosulphate was found to stimulate enzyme systems oxidating any of these compounds. Sulphite and sulphate were ineffective in this respect. The oxidation of elemental sulphur was stimulated by CaCO3, technical urea and high doses of superphosphate and potassium sulphate. It was inhibited by KH2PO4, pure urea, 40 % potassium salt, ammonium nitrate with calcium carbonate and the fertilizer NPK I. It proceeded at the highest rate at approximately 60 % capillary capacity (61 % of mass water content). Oxidation of thiosulphate was stimulated by KH2PO4, pure urea, superphosphate, potassium sulphate and only slightly by the fertilizer NPK I. It was inhibited by CaCO3, 40 % potassium salt and only slightly by ammonium nitrate with calcium carbonate. Potassium chloride, glucose and technical urea were without effect. The oxidation proceeded at the highest rate at 35 % maximal capillary capacity (48 % mass water content).
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PMID:Some factors influencing production of sulphate by oxidation of elemental sulphur and thiosulphate in upper horizons of spruce forest soils. 626 35

A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity. Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead 1a. Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyrido[3,4-b]pyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists. Among the compounds synthesized, N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N,7-dimethyl-8-oxo-5- (substituted phenyl)-6-pyrido[3,4-b]pyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of [125I]-BH-SP binding in human IM-9 cells) of 0.21-0.34 nM and ED50 values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg. These compounds exhibited significantly potent activity upon oral administration with ED50 values of 0.068-0.17 mg/kg. Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.
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PMID:Novel, potent, and orally active substance P antagonists: synthesis and antagonist activity of N-benzylcarboxamide derivatives of pyrido[3,4-b]pyridine. 754 79

The effects of systemically-administered human alpha calcitonin gene-related peptide (h.alpha CGRP), substance P and the selective neurokinin receptor agonists, GR73632 (NK1) and GR64349 (NK2) on cerebral blood flow (CBF) were studied in anaesthetized guinea-pigs using a laser-Doppler flowmeter. h.alpha CGRP (0.1 and 0.3 nmol/kg), substance P (0.03-1.0 nmol/kg), GR73632 (0.03-0.3 nmol/kg) and GR64349 (0.3 nmol/kg) each, following intra-carotid artery injection, reduced transiently (< 5 min) blood pressure and CBF. GR73632 (0.1 and 0.3 nmol/kg) and GR64349 (0.3 nmol/kg), but not h.alpha CGRP (0.01-0.3 nmol/kg) or substance P(0.01-1.0 nmol/kg), then produced a more prolonged increase in CBF, the peak effect occurring 10-15 min after injection. It is likely that this increase in CBF was due to their bronchoconstrictor activity, rather than a direct effect on the cerebrovasculature; arterial PaCO2 levels were increased and PaO2 decreased by both compounds. Following pretreatment with urea (5 M) to disrupt the blood brain barrier, h.alpha CGRP (0.1 nmol/kg) produced a significant increase in CBF (13 +/- 4%), implying that access to its receptors on the cerebrovascular smooth muscle had been achieved. Substance P (0.1 nmol/kg) remained inactive. The study has demonstrated that compounds acting on neuropeptide receptors have little direct influence on CBF following systemic administration. CGRP requires access to its receptors on the cerebrovascular smooth muscle, while selective NK1 and NK2 receptor agonists increase CBF, probably indirectly via their bronchoconstrictor activity. The lack of effect of substance P may be due to its rapid breakdown by peptidases, a property not shared by the selective neurokinin agonists.
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PMID:The influence of neurokinins and calcitonin gene-related peptide on cerebral blood flow in anaesthetized guinea-pigs. 768 75

The use of a dipeptide library as the source of a micromolar chemical lead compound for the human tachykinin NK3 receptor is described. The screening of a dipeptide library through a cloned human NK3 receptor binding assay resulted in the identification of Boc(S)Phe(S)PheNH2 (1), which has subsequently been developed, following a 'peptoid' design strategy, into a series of high-affinity NK3 receptor selective antagonists. The structure-activity relationship of the C-terminal portion of this dipeptide lead was first explored and led to the identification of the urea derivative Boc(S)Phe(R)alphaMePheNH(CH2)7NHCONH2 (41, PD157672). This modified dipeptide has a Ke of 7 nM in blocking senktide-induced increases in intracellular calcium levels in human NK3 receptors stably expressed in CHO cells. Subsequent optimization of the N-terminal BocPhe group and the alphaMePhe residue side chain of 41 led to the identification of [S-(R*,S*)]-[2-(2,3-difluorophenyl)-1-methyl-1-[(7-ureidoheptyl)ca r bamoyl]ethyl]carbamic acid 2-methyl-1-phenylpropyl ester (60, PD161182), a non-peptide NK3 receptor selective antagonist. Compound 60 blocks the senktide-evoked increases in intracellular calcium levels in cloned human NK3 receptors stably expressed in CHO cells with Ke of 0.9 nM.
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PMID:Use of a dipeptide chemical library in the development of non-peptide tachykinin NK3 receptor selective antagonists. 864 6

We studied the influence of dietary L-arginine (L-ARG) supplementation on forearm resistance arteries in vivo and the effect of exogenous addition of L-ARG to subcutaneous arteries isolated from gluteal biopsies. Twenty-six healthy males were recruited, and 16 were randomly allocated in a double-blind protocol to receive either oral L-ARG 20 g/day or placebo for 28 days. We examined responses to acetylcholine (ACh), sodium nitroprusside (SNP) and NG-monomethyl-L-arginine (L-NMMA) on forearm resistance arteries using venous occlusion plethysmography performed before and after supplementation of L-ARG (or placebo). L-ARG 20 g/day had no effect on plasma L-ARG levels (% mol based on total amino acid pool; before vs. after L-ARG 3.43 +/- 0.31 vs. 3.76 +/- 0.05), weekly blood pressure (BP) measurements, or plasma biochemical analysis of liver function enzymes, urea, or electrolyte levels. On the other hand, analysis of the major amino acids in plasma showed a significant difference in profile after L-ARG, but not placebo supplementation (Mann Whitney U test, p < 0.05), indicating a domino effect of chronic oral L-ARG supplementation on other amino acids. This may result from a change in appetite and thus protein intake after L-ARG supplementation. At the dose given, neither L-ARG nor placebo had any effect on forearm blood flow (FBF) responses to ACh (area under the dose-response curve, before vs. after L-ARG 1,763 +/- 260.1 vs. 1,862.8 +/- 163.6 U, Student's paired t test; p > 0.05), SNP, or L-NMMA. Gluteal skin biopsies were performed on 10 different untreated subjects. Subcutaneous arteries were isolated and mounted as ring preparations in isometric small vessel myographs. Full concentration-response curves to norepinephrine (NE), ACh, substance P, and a single response to SNP (10 microM) were obtained with and without addition of either L- or D-ARG 10 microM. Both L-ARG [-log EC50 (M) before vs. after arginine 7.12 +/- 0.15 vs. 6.66 +/- 0.16, Student's paired t test, p < 0.005] and D-ARG [-log EC50 (M) before vs. after arginine 7.36 +/- 0.17 vs. 6.85 +/- 0.18; Student's paired t test, p < 0.05] significantly antagonized responses to NE in subcutaneous arteries isolated from healthy humans. With the exception of a subset of vessels in which some endothelial dysfunction was observed, neither of the isomers of arginine had any effect on the responses to ACh, substance P, or SNP. In the subset vessels already described (n = 5), in which responses to ACh were < 90% maximal dilatation, L- but not D-ARG significantly increased the potency to ACh [-log EC50 (M) before vs. after L-ARG 7.42 +/- 0.20 vs. 8.27 +/- 0.28. Student's paired t test, p < 0.05]. We conclude that oral supplementation with L-ARG 20 g/day for 28 days does not affect endothelial function in normal healthy adults, possibly because the dose given in the current study was inadequate or because chronic oral administration leads to dissipation of arginine to other pathways, as evidenced by the change in total amino acid profile but not L-ARG plasma concentration, or because L-ARG cannot improve normal endothelium-mediated vasodilatation. These concepts are supported by our findings that responses to ACh and substance P were not altered by L-ARG in subcutaneous arteries isolated from healthy subjects.
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PMID:Effects of in vivo and in vitro L-arginine supplementation on healthy human vessels. 879 50

The effect of dimethyl sulfoxide (DMSO) on the slow ventral root potential, which is related to nociceptive transmission, was investigated in the isolated spinal cord of a newborn rat. DMSO at 0.3-1% (v/v) enhanced the slow ventral root potential, but not mono- and polysynaptic reflex discharges. DMSO at 1% also enhanced the depolarization induced by substance P or capsaicin. In the presence of tetrodotoxin (0.3 microM), DMSO at 1% did not influence the substance P-induced depolarization but enhanced the acetylcholine-induced depolarization. Edrophonium at 10 microM also enhanced the slow ventral root potential, and the magnitude of the effect was comparable to that of 1% DMSO. In the presence of atropine (0.3 microM) and hexamethonium (30 microM), the effect of edrophonium disappeared, but half of the effect of DMSO remained. Artificial cerebrospinal fluid containing either 0.87% (w/v) urea or 4.6% (w/v) sucrose, which has the same osmotic pressure as that containing 1% DMSO, did not have the same effect as DMSO on the slow ventral root potential. In the saphenous nerve-dorsal root preparation, the compound action potential was enhanced by 4-aminopyridine (10 microM), but was not affected by DMSO up to 3%. The results suggest that DMSO enhances the slow ventral root potential through mechanisms based on the inhibition of cholinesterase activity and other action(s) involved in increasing transmitter release from nerve endings in nociceptive transmission pathways in the isolated spinal cord of the newborn rat. Neither the blockade of K+ channels nor hyperosmotic effects are likely mechanisms of DMSO action.
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PMID:Enhancing effect of dimethyl sulfoxide on nociceptive transmission in isolated spinal cord of newborn rat. 968

The use of compost or manure in agriculture as an organic source of nutrients is common in many tropical, developing countries like Nigeria. One of the drawbacks of such materials is their low nitrogen (N) content (=1% N). Farmers commonly use chemical N fertilizers such as urea, calcium ammonium nitrate (CAN), and NPK formulations to obtain better crop growth and yield. These chemical supplements may have a negative impact on the environment through nitrate leaching into water, leading to eutrophication of surface waters that can affect public health. Gliricidia sepium, a fast-growing, tropical, perennial hedge plant was tested as a source of N in organo-mineral fertilizer formulations. Average nutrient content of Gliricidia is 3.8% N, 0.32% P, 1.8% K, 0.8% Ca, and 0.2% Mg. Using a sand culture and Amaranthus caudatus as a test crop, it was shown that amending commercial composts with 30% Gliricidia prunings would benefit many small-scale farmers and control environmental pollution.
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PMID:Alternate nitrogen amendments for organic fertilizers. 1280 38

We studied the suitability of municipal solid waste compost (MSWC) application to submerged rice paddies in the perspective of metal pollution hazards associated with such materials. Experiments were conducted during the wet seasons of 1997, 1998 and 1999 on rice grown under submerged condition, at the Agriculture Experimental Farm, Calcutta University at Baruipur, West Bengal, India. The treatments consisted of control, no input; MSWC, at 60 kgNha(-1); well decomposed cow manure (DCM), at 60 kgNha(-1); MSWC (30 kgNha(-1)) +Urea (30 kgNha(-1)); DCM (30 kgNha(-1)) +U (30 kgNha(-1)) and Fertilizer, (at 60:30:30 NPK kgha(-1) through urea, single superphosphate and muriate of potash respectively). Soil microbial biomass-C (MBC), MBC as percentage of organic-C (ratio index value, RIV), urease and acid phosphatase activities were higher in DCM than MSWC-treated soils, due to higher amount of biogenic organic materials like water soluble organic carbon, carbohydrate and mineralizable nitrogen in the former. The studied parameters were higher when urea was integrated with DCM or MSWC, compared to their single applications. Soil MBC, urease and acid phosphatase activities periodically declined up to 60 day after transplanting (DAT) and then increased after crop harvest. The heavy metals in MSWC did not detrimentally influence MBC, urease and acid phosphatase activities of soil. In the event of long term MSWC application, changes in soil quality parameters should be monitored regularly, since heavy metals once entering into soil persist over a long period.
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PMID:Microbial biomass and enzyme activities in submerged rice soil amended with municipal solid waste compost and decomposed cow manure. 1592 49

Capsaicin-sensitive afferent nerves (CSANs) are involved in the protection of gastric mucosa. To clarify the role of CSANs in human Helicobacter pylori-negative or -positive chronic gastritis, after bacterium detection by rapid urease test, (14)C urea breath test, and specific histological staining, the immunodistribution of capsaicin receptor, calcitonin gene-related peptide (CGRP), and substance P (SP) was studied in 21 H. pylori-positive and 30 H. pylori-negative patients with chronic gastritis and 20 patients with functional dyspepsia (as histologically healthy controls). The expression of capsaicin receptor, CGRP, and SP was significantly higher in the mucosa of patients with chronic gastritis than in controls, however, no significant difference was obtained in the immunodistribution in patients with H. pylori-negative versus H. pylori-positive gastritis. In conclusion, CSANs participate in the development of human gastritis, however, their participation does not depend on the presence of Helicobacter pylori as a causative factor.
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PMID:Participation of capsaicin-sensitive afferent nerves in the gastric mucosa of patients with Helicobacter pylori-positive or-negative chronic gastritis. 1719 20


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