UNIPROT:P20366 - FACTA Search

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)

Thermal injury to one hind limb of rats was induced by immersion into water at 62 degrees C. Both a mild (15 s) or severe (30 s) lesion caused inflammation of the limb when observed 24 h later; but at this time the animals used the injured limb when they walked. Animals with a severe lesion of the injured limb subsequently withdrew it from use when walking. Limb withdrawal did not occur following a mild lesion. At 24 h following the lesion, lumbar spinal cord levels of [Met]enkephalin, as measured by radioimmunoassay, were elevated (70%) bilaterally in both hemisegments, ipsi- and contralateral to the lesion. At seven days following either mild or severe hind limb lesion [Met]enkephalin levels were elevated only in the ipsilateral lumbar hemisegment. At that time no changes in thoracic [Met]enkephalin levels were observed. Substance P levels were decreased (20-25%) bilaterally in the lumbar cord 24 h following a severe limb lesion, but no change was observed at seven days in any cord segment following a mild or severe lesion. Changes in spinal cord [Met]enkephalin content occur in response to thermal injury to one hind limb. However, the changes do not appear to be related to the withdrawal of the damaged limb from use following a severe lesion. Peptide changes in the spinal cord may reflect pain or injury to the damaged limb following a thermal lesion. In contrast, limb withdrawal may be a physiological rest mechanism related to altered basal ganglia peptide function.
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PMID:Increased [Met]enkephalin and decreased substance P in spinal cord following thermal injury to one limb. 170 Mar 32

The molecular properties of substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met amide) and three of its antagonists were derived by measuring the Gibbs adsorption isotherm, providing information on the surface activity, the molecular shape, and the pK values of the different molecules. The following three antagonists were investigated: [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, ANT I; [D-Arg1,D-Trp7,9,Leu11]SP, ANT II and [D-Pro2,D-Trp7,9]SP, ANT III. SP is only moderately surface active. The amino acid substitutions lead, however, to an increased surface activity of the antagonists. From the concentration dependence of the surface activity it was possible to quantify the packing characteristics of the individual neuropeptides. SP shows cross-sectional areas of 300 +/- 5 A2 to 240 +/- 5 A2 (pH 5 to 8, 154 mM NaCl) at concentrations below 10(-5) M, i.e., in the physiological concentration range, indicating a folded SP conformation. Upon increasing the packing density to concentrations larger than 10(-5) M the surface area was only half as large (148 +/- 5 A2 to 124 +/- 3 A2) suggesting now a relatively extended conformation of the SP molecule with its long molecular axis perpendicular to the air/water interface. In contrast, the three antagonists were characterized by surface areas of 147 +/- 3 A2 to 126 +/- 3 A2 which were almost independent of concentration. The antagonists thus adopt a relatively extended conformation in the whole concentration range measured. This is further supported by computer modelling which shows that the antagonists are motionally restricted and can adopt neither a bent nor a alpha-helical conformation. The surface activity of the neuropeptides was dependent on the pH of the solution. At low peptide concentrations (about 10(-6) M) it was possible to resolve and determine the pK values of all individual charged amino acid side chains. The pK values observed for the neuropeptides were about two pK units lower than those of the free amino acids in solution. The pK shifts of the neuropeptides at the air/water interface are explained in terms of the Gouy-Chapman theory. SP and its antagonists bind to lipid bilayers in the order of their surface activity. While the binding of SP is mainly due to electrostatic interactions, hydrophobic peptide-lipid interactions contribute to the binding of the antagonists.
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PMID:Substance P and antagonists. Surface activity and molecular shapes. 170 20

It has been assumed that the histamine release from mast cells induced by various neuropeptides or basic protein plays some important roles in the development of the hyperreactivity of airways. In the present study, the mechanisms of the histamine release induced by neuropeptides and histone were investigated. Substance P, somatostatin, neurotensin or histone induced histamine release from isolated rat peritoneal mast cells even in the Ca free medium; Ca2+ release from intracellular Ca store was detected very significantly. In order to study the interaction between neuropeptides and phospholipid bilayer of cell membrane, model membrane systems were used. It was indicated that the interaction between basic amino acid residues of neuropeptides and acidic portion in the lipid bilayer caused the conformational changes of neuropeptides from the random coil in the water to the beta-form in the lipids. At the same time, hydrophobic amino acid residues may interact with the hydrophobic region in the lipid bilayer of cell membrane and induce the membrane perturbation, which may cause an increase of the permeability of the membrane. Subsequently, it became evident that after an increase in intracellular Ca2+ concentration, the cytoskeletons inside the mast cell were activated so as to extrude the granules out of the cell.
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PMID:[Mast cell]. 170 50

In order to understand the role of substance P (SP) in the brain and the relationship between SP and enkephalins in the electroacupuncture analgesia (EA), we have observed the influence of SP-antagonist, (D-Arg', D-Phe5, D-Trp7.9, Leu11) -SP (DADPDTL) injected intracerebroventricularly (icv) on EA and the change of the level of SP in the brain regions of the rat during EA. We have made a further observations on the influences of the naloxone (NX) on the che change of the content of SP induced by EA and DADPDTL on the increase in Leu-enkephalins (LEK) induced by EA. The Wistar rats were used in the experiment. The latency of the tail flick, immersing the tip of rat tail (4 cm) into hot-water of 50 degrees C, was taken as the pain threshold. The drugs were injected icv via plastic cannulae implanted in the bilateral ventricles. The EA was applied to the point of "Zusanli" (S36). The contents of SP and LEK were determined radioimmunoassay in the hypothalamus, mid-brain, striatum and pons-medulla-oblongata. The pain threshold was increased by 48 +/- 9% (P less than 0.01) after EA. But icv injection of DADPDTL decreased the pain threshold by 14 +/- 7% after EA. The result suggests that DADPDTL can antagonize the effect of EA and that SP in the brain is involved in EA. After EA the contents of SP in the hypothalamus and mid-brain of the rats were decreased by 29% and 28% in comparison with that of the control group respectively (both of them, P less than 0.05), but the contents of SP in the striatum and pons-medulla-oblongata had no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of substance P in electroacupuncture analgesia and its relation to enkephalins in the rat brain]. 170 61

In this experiment, the rats treated with capsaicin (50 mg/kg) s. c. on day 2 of liqe were used 12 weeks after injection. The levels of substance P(SP) in sciatic nerves and dorsal spinal cords were measured with radioimmunoassay to evaluate the extent of C-afferent fibers damaged by capsaicin. The results as follows: (1) the levels of SP in the sciatic nerve and the dorsal spinal cord are decreased by 69% and by 62% respectively, indicating the degeneration of the primary C-afferent fibers is very massive; (2) the average of basal tail-flick latency (immersing in 50 degrees C water) is prolonged 105% as compared with the control; (3) after electro-acupuncture, the average of tail-flick latency of the capsaicin treated rats is increased by 81%, while that of the vehicle treated rats increased by 54%. These data suggest that C-afferent fibers substantially mediate the transmission of noxious thermal stimuli, but is unnecessary for the transmission of acupuncture message to induce analgesia.
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PMID:[Relation of capsaicin-sensitive neurones to the effect of electro-acupuncture analgesia]. 170 63

A determination of the solution conformational behavior of two tachykinins, substance P and physalaemin, is described. Two-dimensional homonuclear Hartmann-Hahn (HOHAHA) and rotating-frame cross relaxation spectroscopy (ROESY) are used to obtain complete proton resonance assignments. Interproton distance restraints obtained from ROESY spectroscopy are used to characterize the conformational behavior. These data show that in solution both substance P and physalaemin exist in a mixture of conformational states, rather than as a single three-dimensional structure. In water both peptides prefer to be in an extended chain structure. In methanol, their behavior is described as a mixture of beta-turn conformations in dynamic equilibrium. Solvent titration data and chemical shift temperature coefficients complement the NMR estimate of interproton distances by locating hydrogen bonds and serving to identify predominant conformational states. The C-terminal tetrapeptide segment has the same conformational behavior for both substance P and physalaemin. In physalaemin, the midsegment of the peptide may also be constrained by formation of a salt bridge. The conformational behavior of substance P and physalaemin is discussed in relation to potency and receptor binding properties.
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PMID:Conformational analysis of the tachykinins in solution: substance P and physalaemin. 171 36

The present study evaluated the effect of the intracerebroventricular injection of the tachykinins, substance P, neurokinin A and [Asp5.6,MePhe8]substance P(5-11) (also referred to as NH2-senktide), on the alcohol intake of genetically selected, alcohol-preferring rats. Animals were offered both water and 8% ethanol 2 h/day; tachykinins were administered just before access to fluids. Neurokinin A and substance P did not modify alcohol intake at doses up to 1000 and 2000 ng/rat, respectively. On the other hand, NH2-senktide potently suppressed alcohol intake at doses of 31.2-500 ng/rat. At the same doses, however, it did not significantly affect water intake. This finding suggests that its effect on alcohol intake might be rather selective and not due to general impairment of the behavior. Activation of tachykinin NK-3 receptors, for which NH2-senktide is a highly selective agonist, produces angiotensin II release in the brain; however, the effect of NH2-senktide on alcohol intake is probably not mediated by angiotensin II, as suggested by the fact that it is not modified by captopril pretreatment.
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PMID:The tachykinin NH2-senktide inhibits alcohol intake in alcohol-preferring rats. 171 9

This study examined effects of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), on facilitation of the tail flick reflex (1) by intrathecal administration of 6.5 nmol of substance P at the lumbar spinal level in awake rats and (2) by noxious cutaneous stimulation in anesthetized rats (by immersing the tip of the tail in hot water at 55 +/- 1 degrees C for 1.5 min). Reaction time was decreased by about 70% by intrathecal administration of substance P and by about 40% by tail immersion. Intrathecal administration of APV (2 nmol) or cerebrospinal fluid (CSF) failed to alter the baseline responses. However, APV but not CSF blocked the facilitation induced by intrathecal administration of substance P and by tail immersion. These results indicate that while NMDA receptors do not appear to be involved in mediating the tail flick reflex, they may be involved in expression of the facilitation of this reflex by substance P and/or by a related peptide.
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PMID:NMDA receptor antagonist blocks the facilitation of the tail flick reflex in the rat induced by intrathecal administration of substance P and by noxious cutaneous stimulation. 171 54

In this study chromatographic, immunochemical, and immunocytochemical methods provide evidence of a galanin-like peptide(s) in an invertebrate, the blowfly Phormia terraenovae. The major portion of the galanin-like immunoreactivity (GAL-LI) in fly heads was extractable in acetic acid but not in boiling water, which suggests that the peptide(s) may be highly basic in nature. GAL-LI was present both in the head and body portion of the blowfly in roughly the same amounts. Initial gel filtration data, using a G-50 Sephadex column and a weak phosphate-buffer (pH 6.5) as eluent, suggested that a fly GAL-LI peptide(s) from fly heads, eluting as an apparent single peak, was smaller than porcine GAL(1-29) and GAL(1-15). However, concomitant analysis using a G-25 Sephadex column and acetic acid (0.2 M) as eluent, spread the immunoreactive material over a great portion of the chromatogram, although the main portion of the material eluted in the same size range as porcine GAL(1-29). Taken together, the gel filtration data thus suggest that fly GAL-LI peptide(s) may be highly basic but presumably similar in size to vertebrate GAL(1-29). However, the hydrophobic properties of the fly GAL-LI peptide(s) differ from that of porcine GAL as demonstrated by the presence of several immunoreactive components eluting both early as well as late in the chromatogram when using reverse-phase high performance liquid chromatography (HPLC); early peaks may represent highly basic and/or possibly smaller GAL-immunoreactive peptide(s), whereas later peaks may represent less basic and possibly elongated forms. Immunocytochemistry indicated that GAL-LI was present in the nervous system of the blowfly. About 160 GAL-immunoreactive neurons were found in the brain and subesophageal ganglion, 26 in the fused thoracic ganglion and 30 in the fused abdominal ganglion. In the brain, GAL-immunoreactive fibers supply specific subdivisions of the central body, optic lobe, superior protocerebrum, and tritocerebrum as well as neuropil in the subesophageal ganglia. In the thoracico-abdominal ganglia, GAL-immunoreactive neuron processes are found inside synaptic neuropil as well as in the neural sheath of the ganglia and several of the dorsal nerve roots. Many of the GAL-immunoreactive neurons react also with an antiserum against porcine galanin message associated peptide, a peptide present in the preprogalanin protein. Immunocytochemical double-labeling indicated that some GAL-immunoreactive neurons also reacted with antisera against the molluscan peptides FMRFamide and SCPB, whereas no evidence could be found for colabeling with antisera against tyrosine hydroxylase, substance P and physalaemin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Galanin immunoreactivity in the blowfly nervous system: localization and chromatographic analysis. 172 Jul 94

To investigate the participation of neuropeptides present in the peripheral endings of primary afferent neurons in the inflammatory response, immunoreactive substance P (iSP), calcitonin gene-related peptide (iCGRP) and neurokinin A (iNKA) levels in the s.c. perfusate, and inflammatory response (edema and plasma protein extravasation) evoked in rat paw by noxious stimulation were determined. The effects of these peptides on plasma protein extravasation in the skin of the hind paw of mice were also examined with the pontamine sky blue protein labelling method. The following results were obtained. 1) Immersion of the rat hind paw for 30 min into hot water adjusted to 47 degrees C led to a marked increase in the release of iSP and iCGRP in the subcutaneous perfusate with the formation of thermal edema. 2) Mechanical stimulation (600 g, 10 min) to the hind paw or electrical stimulation of the saphenous and sciatic nerves (10 V, 2 Hz, 1msec duration, 10 min) evoked the increase of iSP release in the perfusate with plasma protein extravasation. 3) iNKA release was not affected by neither heat nor mechanical stimulation. 4) Intraplantar injection of SP, CGRP and NKA induced plasma protein extravasation, the order of potencies being SP greater than CGRP greater than NKA. The action of SP was antagonized by spantide, an SP antagonist. The injection of CGRP with SP produced a synergistic action on plasma protein extravasation. 5) Neonatal pretreatment with capsaicin, which is known to degenerate small-diameter primary afferent neurons, caused the decrease in amount of iSP and iCGRP released during noxious heat stimulation. 6) Pretreatment with Compound 48/80, or stem bromelain and emorphazone, or des-Arg9-[Leu8]-BK, inhibited the iSP release evoked by noxious heat stimulation. 7) Opioids such as morphine (mu-agonist) and ethylketocyclazocine (kappa agonist) inhibited the heat stimulus-evoked iSP release and thermal edema, and the inhibitory effects were antagonized by pretreatment with their antagonists. 8) Morphine or ethylketocyclazocine or [D-Ala2,D-Leu5]-enkephalin (delta-agonist) inhibited the release of iSP evoked by electrical stimulation of the saphenous and sciatic nerves. These results indicate that SP and CGRP present in peripheral endings of small-diameter primary afferent neurons play an important role in the inflammatory response, and that opioids are involved in the regulation of inflammatory response through the inhibition of SP release.
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PMID:[A pharmacological study of the participation of the peripheral endings of primary afferent neurons in the inflammatory response evoked by heat and mechanical noxious stimulation]. 172 88

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