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)

We have studied the presence of five neuropeptides in knee joint synovial fluid from either patients suffering from rheumatoid arthritis and pain (n = 18) or being subjected to arthroscopy due to meniscal/cruciate ligament injuries (n = 13). Radioimmunoassay technique was used for peptide analysis using antisera SP2 against substance P (SP), K12 against neurokinin A (NKA), CGRPR8 against calcitonin gene-related peptide (CGRP), NPY1 against neuropeptide Y (NPY) and VIP2 against vasoactive intestinal polypeptide (VIP). No SP could be detected, and lower levels of NKA was found in arthritic joints vs controls. CGRP and NPY was found in higher concentrations in arthritic patients vs controls. VIP was found sporadically in both arthritis and control patients. Our data show some quantitative differences between patients suffering rheumatoid arthritis and pain, and patients with non-inflamed joints without pain; indicating an involvement of peptidergic fibers in arthritis in humans.
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PMID:Concentration of substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid from knee joints in patients suffering from rheumatoid arthritis. 194 95

The occurrence of tachykinins in sensory neurons of the guinea-pig was studied by means of radioimmunoassay combined with ion-exchange and high-performance liquid chromatography as well as by immunohistochemistry. Antisera raised against kassinin (antiserum K12), neurokinin A (NKA) (antiserum NKA2) and substance P (SP) (antisera SP25 and SP2) were used. Antiserum K12 detected NKA, neuropeptide K (NPK) and a component eluting in the position of eledoisin (ELE) in extracts of the lung and ureter. Neurokinin B (NKB) was, however, not found. Neutral water extraction favored recovery of NKA and of the ELE-like component, while NPK was found only in acid extracts. The SP antisera detected two immunoreactive components of which the major form coeluted with synthetic SP. Capsaicin pretreatment depleted all these various forms of immunoreactivity in several peripheral organs including the ureter and lung. The immunoreactivity detected by antisera K12 or SP25 in radioimmunoassay had a similar regional distribution pattern in peripheral tissues. Immunohistochemical examination revealed that antiserum NKA2 stained the same spinal ganglion cells as the SP2 antiserum. The distribution of capsaicin-sensitive nerve fibers stained by these two antisera was also identical in peripheral organs such as the ureter, inferior mesenteric ganglion, heart and lung. It is concluded that multiple tachykinins, including SP, NKA, NPK and an ELE-like peptide, are present in capsaicin-sensitive sensory nerves in the guinea-pig. This finding can most likely be related to the origin of SP, NKA and NPK from the same precursor molecule, subsequent posttranslational tissue processing and axonal transport to terminal regions.
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PMID:Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. 241 71

The presence of substance P in numerous mammalian pineal glands prompted us to search for its binding sites in the bovine pineal gland. The binding assays to pineal membrane were carried out in polypropylene microcentrifuge tubes in a final volume of 500 microliters of 50 mM Tris-HCl buffer (pH 7.4) containing aliquots of 200-500 micrograms protein, 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, and 50 microliters of [3H]substance P (3H-SP, 45.7 Ci/mmol to yield a final concentration of 0.02-20 nM) to start the reactions, which were incubated for 20 min at 20 degrees C. The reactions were terminated by centrifugation in a Fisher Microcentrifuge Model 235A for 30 seconds at 13,000 X g, and the pellets were washed twice with 1 ml of ice-cold 50 mM Tris-HCl buffer containing 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, and 1 mM CaCl2. The bottoms of the tubes were cut, the membrane pellets were dissolved in 5 ml of Triton X-100/toluene fluor (1:3) scintillation fluid, and the radioactivity was counted. The specific [3H]-substance P binding at 1-2 nM was 40-50% of the total binding, and the non-specific binding was assessed by using 2 microM of unlabelled substance P. These studies identified in bovine pineal gland a high affinity receptor site for [3H]SP with a KD value of 0.43 nM and a Bmax value of 71.14 fmol/mg protein. The relative affinity of various substance P analogues or fragments was: substance P greater than physalaemin greater than SP2-11 greater than SP3-11 greater than SP4-11 greater than SP6-11 greater than substance K = eledoisin greater than kassinin greater than SP7-11 greater than SP free acid. Substance P did not alter the basal or the norepinephrine-induced stimulation of the activity of serotonin N-acetyltransferase in rat pineal gland in culture.
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PMID:Studies on high-affinity [3H]substance P binding sites in bovine pineal gland. 243 Jul 88

In the present work we have studied the occurrence of different tachykinins (substance P (SP), neurokinin A (NKA) and neuropeptide K (NPK)) in human distal bronchi and pulmonary arteries by means of radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). We have also compared the biological effects of different tachykinins on isolated human bronchi and pulmonary arteries in vitro. The concentration of immunoreactive SP using antiserum SP2 in the pulmonary arteries was higher (1.34 +/- 0.15 pmol/g) than in the bronchi (0.56 +/- 0.05 pmol/g). The contents of other tachykinins than SP measured using antiserum K12 was on the other hand considerably higher in the bronchi (0.33 +/- 0.14 pmol/g) than in pulmonary arteries (0.13 +/- 0.02 pmol/g). Immunoreactive materials corresponding to SP, NKA and NPK were identified in bronchial extracts by RIA combined with HPLC, which also indicated the presence of an eledoisin (ELE)-like component. In vitro studies showed that NKA was the most potent of the tachykinins as a bronchoconstrictor agent, being several hundred-fold more active than SP, acetylcholine and histamine. NPK had an intermediate potency. The bronchoconstrictor effect of NKA was unaffected by atropine, mepyramine and cimetidine. The tachykinins SP and NKA had on the other hand, a rather equal potency in inducing relaxation of serotonin precontracted pulmonary arteries. In conclusion, multiple tachykinins are present in lower airways of man. These peptides exert different biological activities whereby NKA is a very active bronchoconstrictor agent compared to SP while both NKA and SP have rather similar relaxatory activities of vascular smooth muscle.
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PMID:Occurrence and effects of multiple tachykinins; substance P, neurokinin A and neuropeptide K in human lower airways. 243 21

The ability of the SP fragments SP2-11 and SP3-11 to release histamine from rat peritoneal mast cells has been compared with that of the whole peptide. SP1-11 was found to be about 3.4 times more active than SP2-11 and about 10.4 times more active than SP3-11. The substance P antagonist [D-Pro4, D-Trp7,9,10] SP4-11 was equally effective at antagonizing the histamine releasing action of SP1-11, SP2-11 and SP3-11. Benzalkonium chloride was found to be a competitive antagonist of SP and SP3-11: the dissociation constants for the benzalkonium chloride-receptor interaction being about the same when either SP1-11 or SP3-11 was used as the agonist.
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PMID:Action of the SP2-11 and SP3-11 fragments of substance P on rat peritoneal mast cells. 244 Feb 65

1. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
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PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

A reversed-phase high-performance liquid chromatographic procedure combined with radioimmunoassay (HPLC-RIA) was developed and optimized for the concomitant quantitation of substance P (SP) and some of its C- and N-terminal fragments in the extracts of the spinal cord of mice. A selective and efficient solid-phase extraction protocol was used for preparative purification of sample homogenates prior to analyses. The sensitivity of the HPLC assay was 18.75 ng for SP and some of its fragments of interest. Recoveries of peptides were calculated from spiked aqueous standards carried through the experimental protocol and ranged from 53 to 98%. The precision of the peptide recoveries from aqueous-based standards, expressed as coefficient of variation, ranged from 2 to 28%. The sensitivities for the RIA procedure using SP antiserum were 1.5, 3.4 and 4.6 fmol SP1-11, SP2-11 and SP5-11, respectively. The percentage cross-reactivity of SP1-11 antiserum with the C-terminal fragments was complete whereas the cross-reactivities of the N-terminal fragments were essentially zero. The molar limits of detectability of SP and some of its C-terminal fragments determined by HPLC alone were several orders of magnitude greater than those determined from the same spinal cord samples using RIA after HPLC fractionation.
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PMID:Optimization of high-performance liquid chromatography-radioimmunoassay protocols for the analyses of substance P and some of its metabolic fragments. 246 6

Previous studies with N-terminal fragments of substance P (SP) have suggested the existence of two separate SP receptor populations. SP1 receptors are found in guinea pig ilea and rat colons. SP2 receptors are found in mouse spinal cords and rat salivary glands. We have now found that substitution of Gly9 in substance P's C-terminal hexapeptide leads to an analog (L-Pro9 SP6-11) which selectively and potently stimulates SP2 receptors. In contrast, substitution of the same residue with D-Proline results in a potent and selective agonist for SP1 receptors. The data dramatically confirm the distinction between SP1 and SP2 receptors and demonstrate that the two receptors have distinct stereochemical architectures.
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PMID:Stereospecificity of SP1 and SP2 substance P receptors. 257 10

We have analysed the concentrations of substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in the synovial fluid from 5 patients suffering from arthritis with inflamed knee joints as well as from 5 healthy control subjects with an earlier traumatic meniscal or cruciate ligament injury. Competitive radioimmunoassay was done using antisera SP2 (SP), K12 (NKA), R8 (CGRP), and NPY1 (NPY). No SP-like immunoreactivity (-LI) was detected in any patient. NKA-LI was found in all control patients but in none of the arthritis patients. CGRP-LI was seen in all arthritis patients as well as in 3/5 control patients, a non-significant difference. NPY-LI was found in a significantly higher concentration in the arthritis group vs the control patients. The results support an involvement of neuropeptides in human joint inflammation.
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PMID:Immunoreactive tachykinins, calcitonin gene-related peptide and neuropeptide Y in human synovial fluid from inflamed knee joints. 278 54

The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.
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PMID:Use of substance P fragments to differentiate substance P receptors of different tissues. 618 Apr 59


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