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)

Acid and neutral proteinases were isolated with the purpose of investigating their participation in the breakdown of hypothalamic peptides and proteins. The acid proteinase was purified about 1000-fold from hypothalamus by precipitation with acetone, chromatography on SP-Sephadex G-50, gel filtration through column of G-100 and chromatography on DEAE-Sephadex A-50. The molecular weight of the enzyme was approximately 50.000. Maximal activity against hemoglobin was obtained at pH 3,2--3,5: serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, benzothonium cloride, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, Substance P and some C-fragments of Substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. Neutral proteinase was isolated from the supernatant fraction(100.000 g) of a 0,3 M sucrose homogenate of bovine hypothalamus by chromatography on DEAE Sephadex A-50, gel filtration through Sephadex G-100 and rechromatography on DEAE sephadex A-50 using luliberin as substrate. The rates of breakdown of luliberin and denaturated hemoglobin were measured by fluorometric estimation of acid-soluble peptides wieht o-phthaldialdehyde. The purifed enzyme preparations have a pH optimum of activity at 7--7,5. The enzymes molecular weight was approximatelyy 30--40.000. Enzyme activity was inhibited by L-1-tosylamide-2-phenylethylchloromethyl ketone, p-chloromercuribenzoate and divalent ions Co2+, Zn2+ and was significantly enhanced by dithiothreitol. The Km values for the reaction of hydrolysis of luliberin and hemoglobin were 1,33.10(-5) and 5,2.10(-5) M respectively. The neutral proteinase from the hypothalamus cleaves luliberin, somatostatin and Substance P. Sites of action of the enzyme upon those peptides were determined by means of the dansyl technique. The acid proteinase, most likely cathepsin D, and neutral proteinase from hypothalamus, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus.
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PMID:[Breakdown of luliberin, somatostatin and substance P as an effect of hypothalamic endopeptidases]. 4 63

1. Substance P (synthetic or extracted for intestine or central nervous system) is devoid of an algesic effect on paravascular pain receptors. 2. The algesic effect of a AP-containing acetone HCl-extract from spinal cord is explained by its high content of potassium ions. 3. SP-containing preparations which include an ammonium sulphate precipitation in the extraction procedure are algesic due to content of this salt. 4. SP-containing extract from intestine were found to be contaminated with a bradykinin-like peptide of high algesic potency. 5. These findings are discussed with regard to the restricted value of earlier results about central actions of SP-containing tissue extracts and with regard to the role of SP as a possible neurotransmitter.
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PMID:Lack of algesic effect of substance P on paravascular pain receptors. 56 91

1. Substance P (SP) was measured in acid acetone extracted plasma of cats using a sensitive radioimmunoassay. The immunoreactive material was submitted to ion exchange chromatography and at least 90% of immunoreactivity co-chromatographed with synthetic SP. 2. The level of immunoreactive SP (I-SP) in extracted plasma of the cat was 69.3 +/- 9.8 fmol/ml with values ranging from 2.5 to 165 fmol/ml. Evisceration of the cats caused a decrease of I-SP levels from 70.8 +/- 30.8 fmol/ml to 20.8 +/- 9.9 15 min and to 26.8 +/- 19.7 fmol/ml 60 min after the operation. 3. Ligation of intestinal blood vessels led to a fall in I-SP levels from 58.7 +/- 11.5 to 25.9 +/- 4.1 fmol/ml within 15 min. 4. No difference between I-SP values in portal (71.8 +/- 11.2 fmol/ml) and peripheral plasma (68.3 +/- 12.1 fmol/ml) was found under the conditions in which these experiments were performed. 5. It is concluded that a major part of circulating immunoreactive SP originates from the intestine.
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PMID:The intestine as source of immunoreactive substance P in plasma of the cat. 72 66

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.
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PMID:Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog. 169 75

The airways receive a dense innervation from sensory neurons containing substance P (SP). An anti-SP anti-idiotypic antibody (anti-Id ab) recognizing SP receptors was previously characterized pharmacologically and proved to be useful in immunohistochemistry of the central nervous system. This antibody was used to localize SP binding sites in the guinea-pig trachea by immunohistochemistry. Immunolabelling was considered as specific when it could be prevented by a) preabsorption of the anti-Id ab with a C-terminal specific monoclonal anti-SP antibody, and b) preincubation of the tissue sections with either of the tachykinins, substance P and neurokinin A, in the presence of the inhibitor of neutral endopeptidase, phosphoramidon, and addition of these compounds into the antibody incubation medium. Moreover, immunofluorescence was absent when the acetone-fixed of fresh frozen sections were exposed to the detergent Tween 20 prior to immunohistochemistry, which points to a membrane localization of the detected tissue antigen, as expected for SP receptors. Compared with previous reports on autoradiographic localization of SP receptors in the guinea-pig trachea, the present immunohistochemical approach proved to be superior in enabling discrimination of labelled elements: Trachealis muscle, cylindrical epithelial cells and some roundish, singly lying cells in the epithelium and subepithelial lamina propria displayed specific immunofluorescence. These morphological findings match well with the known pharmacological actions of SP on the guinea-pig trachea.
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PMID:Immunohistochemistry of the guinea-pig trachea using an anti-idiotypic antibody recognizing substance P receptors. 215 58

The axon reflex flare response to noxious stimulation of the skin is mediated by polymodal nociceptors of "C" fibre primary afferent nerves. Topical application of capsaicin initiates such a flare. The mediator of the response is presumed to be substance P. In this study we examined the flare response to topical capsaicin (1g/L in 70% alcohol for 30 minutes; n = 220) and the substance P content of autopsied skin (3mm punch biopsy; n = 14). The area of the flare response was measured by tracing a Leitz ASM probe onto traced flare outlines. Skin was extracted in acetic acid and acetone and substance P measured by radio-immunoassay. Skin thickness was also measured in parallel biopsy specimens. The flare response decreased with increasing age at sites examined on the trunk and proximal extremities (for the trapezoid ridge r = -0.41; p less than 0.001). The substance P content of skin also decreased with age at those sites examined (for the cubital fossa r = -0.57; p less than 0.05). There was no relationship between age and skin thickness. The results demonstrate decreased activity of the axon reflex mechanism with increasing age. This may be due to changes in substance P containing nerve terminal density. The importance of a reduced neurogenic inflammatory response in the pathology of ageing is unknown.
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PMID:Effects of age on the axon reflex response to noxious chemical stimulation. 243 70

Two cystatins were purified from tissue extract of bovine brain by alkaline treatment, acetone fractionation, gel chromatography on Sephadex G-75, and affinity chromatography on S-carboxymethyl-papain-Sepharose. One of the inhibitors had a relatively high molecular mass, 25 kDa (HMM-cystatin) with pI 4.7, and the other, 11 kDa (LMM-cystatin) with pI 5.23. Both inhibitors showed considerable stability at pH 2 and 80 degrees C. The cystatins inhibited papain, ficin, and cathepsins B and H, but not trypsin, chymotrypsin, thermolysin, nagarse, and cathepsin D. Ki values for the complexes of papain and the inhibitors were estimated to be 2.8 x 10(-10) M for HMM-cystatin and 1.3 x 10(-9) M for LMM-cystatin. Both purified cystatins prevented degradation of substance P by soluble fraction and lysosomal extract obtained from synaptosomes, but did not suppress the cleavage of the peptide by synaptosomal plasma membranes.
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PMID:Cystatins from bovine brain: purification, some properties, and action on substance P degrading activity. 245 27

Five unique, high affinity rabbit polyclonal antibodies against neuromedin B were characterized in a radioimmunoassay in terms of the following parameters: pH and type of buffer, ionic strength, and non-ionic detergents in order to optimize immunoglobulin-peptide interaction; specificity using peptides of the bombesin family, in addition to the tachykinin substance P; and affinity to neuromedin B. Optimum conditions included acidic pH (5.25), high ionic strength (greater than 0.1 M) and absence of non-ionic detergents, which inhibited the assay. Affinities for the 5 antibodies ranged from 10 to 48 fmol neuromedin B with titers from 1:1,000 to 1:10,000 and the sequence-specificity covered the entire peptide; cross-reactivity towards substance P was negligible. As a model tissue, rat spinal cord was homogenized with 5 different extraction solvents, including acetone, methanol, acid and alkaline conditions, and assayed by each polyclonal antiserum; neuromedin B immunoreactivity levels were highest in acid and alkaline extracts and reflected the specificity of the antibody used. Applying these antisera to rat brain extracts, the posterior pituitary gland contained the highest concentration of immunoreactive equivalents of neuromedin B followed by the anterior pituitary, hypothalamus, and hippocampus. The immunoreactive content in the pituitary and hypothalamus, however, depended on the particular antisera used with significant (P less than 0.01) differences existing between them. Further application of these polyclonal antibodies to a spinal cord extract analyzed by isocratic reverse-phase HPLC conditions also revealed differences in their cross-reactivity with the immunoreactive peptides. These antisera may now be used as molecular probes for the determination of extractable immunoreactive neuromedin B from neural tissue and in situ localization by immunohistochemical techniques.
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PMID:Assessment of neuromedin B polyclonal antibodies as molecular probes in neural tissue. 335 56

Acid-acetone extracts of the chicken rectum were subjected to chromatographic and electrophoretic separation, and two new smooth muscle-contracting substances close to purity were obtained. One of them showed chemical and biological characteristics similar to those of substance P, but it was clearly different from substance P on the basis of chromatographic and electrophoretic criteria. Thus, one could be a peptide belonging to the substance P-family. The other substance was also shown to be of peptide nature since its biological activity was destroyed by chymotrypsin and carboxypeptidase A. Parallel bioassay on the two tissues of the longitudinal muscle of the guinea-pig ileum and the isolated whole chick rectum revealed that none of the peptides such as substance P, physalaemin, kassinin, eledoisin, bradykinin and angiotensin II could be a candidate for the active substance. The biological activity was not antagonized by naloxone, suggesting that the substance was a peptide other than the opioid compounds. The molecular sizes estimated by gel filtration are 1300 for the substance P-like peptide and 1600 for the other substance. The possible physiological roles of the two substances as an excitatory non-adrenergic, non-cholinergic transmitter were discussed.
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PMID:Isolation of smooth muscle excitatory substances from chicken rectum and their characterization. 395 45

A new method for extraction of immunoreactive substance P (I-SP) from rat intestine including pulverization of tissue frozen in liquid nitrogen and extraction with acid acetone is described. Using this method, amounts of I-SP in the rat intestine were found to be higher than previously reported. The highest concentrations of I-SP were found in the small intestine. Capsaicin pretreatment of newborn or adult rats had no effect on intestinal I-SP concentrations indicating that intrinsic SP neurones are capsaicin-insensitive.
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PMID:Distribution of substance P in the rat gastrointestinal tract--lack of effect of capsaicin pretreatment. 615 86


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