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)

Human beta (1-40) and rat beta (1-42) were dissolved in three different solvents and stereotaxically injected into rat hippocampus with the contralateral side injected with control reverse sequence peptide or vehicle alone. Results at 1 week showed gross toxicity of the 35% acetonitrile solvent which was markedly enhanced by 3 nmol of beta protein but not by reverse sequence peptide. Beta peptide in water also appeared more toxic than reverse sequence, but the results were less clear cut. In contrast, 3 nmol of beta peptide in a cyclodextrin/PBS solution produced no marked short-term toxic effects. Peripheral injection of substance P failed to prevent toxicity. We conclude that solvent effects play a major role in acute beta protein neurotoxicity.
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PMID:Solvent effects on beta protein toxicity in vivo. 146 48

Lithuania's environment is heavily polluted as a result of domestic and transboundary contamination. The main ecological problems are related to atmospheric pollution; water contamination; soil, water, and forest acidification; nitrogen-compounds overload of soil, water, and food; and contamination with agricultural chemicals and heavy metals. The increased environmental distress is a menace to public health in Lithuania. Experimental studies need to be designed and used to ascertain the effects of environmental distress on the gastrointestinal tract epithelial barrier. Our electronmicroscopic and immunohistochemical study of human gastrointestinal endocrine cells revealed changes in the amount of secretory material and intracytoplasmic vacuolization after exposure to the environmental chemicals such as hexavalent chromium and the herbicide Saprol. The most affected were the EC (serotonin, motilin, substance P), D (somatostatin), A (glucagon), B (insulin), and mast (histamine, serotonin, heparin) cells. These results provide ultrastructural evidence of digestive tract epithelial barrier reaction as an expression of environmental distress signals of the organism.
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PMID:Environmental monitoring in Lithuania. Environmental distress signals: gastrointestinal epithelial barrier after exposure to chemical agents. 146 10

Central injection of the tachykinins (TKs) neurokinin A (NKA), eledoisin (ELE), and kassinin (KASS) produced long-lasting inhibition (up to 6 h) of drinking induced by subcutaneous hypertonic NaCl, while substance P (SP) and physalaemin (PHYS) evoked short-lasting effects. The hypothesis that water retention or increased Na+ excretion by the kidney (induced by TKs) may reduce the need for water ingestion was tested. The results obtained both in urine collection experiments and in nephrectomized rats showed that the duration of the effect of NKA, ELE, and KASS is not due to water retention or increased Na+ excretion by the kidney. The effect of NKA, but not that of ELE and KASS, was shortened by nephrectomy, even though NKA did not modify urine volume or Na+ excretion. Indomethacin pretreatment, like nephrectomy, reduced the duration of the NKA effect, suggesting that renal prostaglandins are involved in it. On the other hand, the long-lasting effect of the three TKs cannot be easily explained in terms of slow metabolic degradation, particularly for NKA. Alternatively, it might be hypothesized that these TKs produce a modification of osmoreceptor function lasting well beyond the life of the peptide, and/or that they produce Na+ loss through emunctories different from the kidney.
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PMID:Inhibition of cell dehydration-induced drinking by tachykinins: evaluation of possible renal effects accounting for the long-lasting inhibition. 152 99

The effects of 1-methyl-4-phenylpyridinium (MPP+) were studied in rat striatum. Using freeze-clamp, microwave, and water-suppressed proton chemical shift magnetic resonance imaging techniques, MPP+ resulted in marked increases in lactate and a depletion of ATP for up to 48 h after the injections. MPP+ produced dose-dependent depletions of dopamine, serotonin, gamma-aminobutyric acid, and substance P that were partially blocked at 1 week by prior decortication or completely blocked by MK-801 at 24 h. The lesions showed relative sparing of somatostatin-neuropeptide Y neurons, consistent with N-methyl-D-aspartate (NMDA) excitotoxicity. MPP+ produces impairment of oxidative phosphorylation in vivo, which may result in membrane depolarization with persistent activation of NMDA receptors and excitotoxic neuronal degeneration. An impairment of energy metabolism may therefore underlie slow excitotoxic neuronal death in neurodegenerative diseases.
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PMID:1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. 156 Feb 46

The present study investigated the effect on water and food intake in the rat of the intracerebroventricular (ICV) injection of neuropeptide K (NPK), the N-terminally extended form of neurokinin A. NPK inhibited water deprivation-induced water intake even at 31.2 ng/rat. At higher doses, it inhibited also water intake induced by ICV angiotensin II or by subcutaneous hypertonic NaCl, and food-associated drinking, the threshold dose being 125 ng/rat. In response to 125 ng/rat, food intake following 16 h food deprivation was not reduced. NPK inhibited food intake only at 500 ng/rat, a dose that evoked excessive grooming in treated animals. Thus NPK is a potent inhibitor of water deprivation-induced drinking and at higher doses it exerts a general antidipsogenic effect towards several dipsogenic determinants, without affecting food intake. On the other hand, it inhibits food intake only at high doses, 500 ng/rat or more, but this inhibition might be just related to the intense grooming evoked. The effects of NPK on ingestive behavior are markedly different from those of neurokinin A, which selectively inhibits osmotic drinking and food-associated drinking. These differences suggest that NPK itself may exert its effects on the central nervous system, not necessarily through the conversion to neurokinin A.
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PMID:Central effects of neuropeptide K on water and food intake in the rat. 159 48

The mechanisms underlying the severe urinary retention induced by acrylamide intoxication were studied in detail in the rat. Subcutaneous treatment with acrylamide monomer (50 mg/kg daily for 10 days) almost completely impaired the micturition reflex, resulting in urinary retention. In fact, the ability to eliminate an oral water load was virtually abolished, while bladder filling with saline (transvesical cystometrogram) failed to activate reflex micturition. Instead, a picture of overflow incontinence resulted in urethane-anaesthetized rats, which was not reversed by intravenous administration of 4-aminopyridine. The nerve-mediated contractile response to field stimulation (0.1-20 Hz, 0.5 ms, 60 V) of the isolated bladder was unaffected, thus suggesting the integrity of bladder efferent innervation, and no evidence was found from in vitro experiments that the myogenic contractility of the bladder was depressed by acrylamide treatment. Conversely, the sensory nerve-mediated response to capsaicin was abolished and sensory nerve fibres of the bladder were selectively depleted of their content of substance P- and calcitonin gene-related peptide immunoreactivity following acrylamide treatment. In fact, concentrations of the same neuropeptides in other organs, including the adjoining ureters, were unaffected. As to the urethral segment, including the striated sphincter, the D-tubocurarine (0.2 mM)-sensitive urethral response to electrical stimulation (0.1 Hz, 0.1 ms, 20 V) was significantly reduced in acrylamide-treated animals. At the same level, neurofilament protein immunostaining revealed striking accumulations of neurofilament protein-like material in motor end-plates, thus indicating that neuromuscular junctions of the urethral striated sphincter were severely affected. Thus, the afferent arm of the micturition reflex was shown to be severely deranged by acrylamide intoxication, especially in its capsaicin-sensitive component. Since twitch-like contractions of the urethral striated sphincter are probably involved in promoting bladder voiding, a decreased efficiency of this mechanism could participate in the picture of urinary retention induced by acrylamide.
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PMID:Acrylamide-induced visceral neuropathy: evidence for the involvement of capsaicin-sensitive nerves of the rat urinary bladder. 164 5

The release of tachykinins and calcitonin gene-related peptide (CGRP) into subcutaneous perfusates was investigated. Immersion of the hind paw of rats in water at 47 degrees C for 30 min led to a marked increase of immunoreactive CGRP (iCGRP) release as well as immunoreactive substance P release, but no detectable increase of immunoreactive neurokinin A release. Neonatal pretreatment with capsaicin or section of the sciatic and the saphenous nerves significantly inhibited the heat stimulation-induced release of iCGRP.
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PMID:Influence of heat stimulation on the amount of calcitonin gene-related peptide and neurokinin A in the subcutaneous space of the rat hind instep. 165 75

NKA (4-10), the C-terminal heptapeptide fragment (Asp-Ser-Phe-Val-Gly-Leu-Met-NH2) of tachykinin NKA, is more active than the parent native compound in the interaction with the NK-2 receptor. Substitution of Gly8 with the more flexible residue beta-Ala8 increases its selectivity with respect to other two known receptors (NK-1 and NK-3), whereas substitution with either D-Ala8 or GABA8 deprives the peptide of its biological activity. These findings can be interpreted by a conformational analysis based on NMR studies in DMSO-d6 and in a DMSO-d6/H2O cryoprotective mixture combined with internal energy calculations. NKA(4-10) is characterized by a structure containing a type I beta-turn extending from Ser5 to Gly8, followed by a gamma-turn centered on Gly8, whereas for [beta-Ala8]NKA(4-10) is possible to suggest a type I beta-turn extending from Ser5 to beta-Ala8, followed by a C8 turn comprising beta-Ala8 and Leu9 and by another beta-turn extending from beta-Ala8 to the terminal NH2. The preferred conformation of [beta-Ala8]NKA(4-10) is not compatible with models for NK-1 and NK-3 agonists proposed on the basis of rigid peptide agonists [Levian-Teitelbaum et al. (1989) Biopolymers 28, 51-64; Sumner & Ferretti (1989) FEBS Lett. 253, 117-120]. The preferred solution conformation of [beta-Ala8]NKA(4-10) may thus be considered as a likely bioactive conformation for NK-2 selective peptides.
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PMID:Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. 165 41

The contribution of C-fiber neuropeptides and excitatory amino acids (EAAs) as central mediators of secondary hyperalgesia was assessed by examining the effects of intrathecal (i.t.) administration of receptor-selective agonists and antagonists on foot-withdrawal latencies (from 48 degrees C water), both before and after heat injury of the contralateral hindpaw. The hyperalgesia which develops in the hindpaw contralateral to a heat injury, could be reproduced in uninjured rats following i.t. injection of substance P, neurokinin A and N-methyl-D-aspartate (NMDA) but not following calcitonin gene related peptide (CGRP), neurokinin B, kainate or (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). Contralateral hyperalgesia was reversed by the substance P antagonist Arg1,D-Pro2,D-Phe2-D-His9-substance P, and the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (APV), but not by the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When the limb of the injured hindpaw was pretreated with the C-fiber neurotoxin capsaicin, hyperalgesia in the contralateral hindpaw was unaffected. Furthermore, prior to injury, the capsaicin pretreatment itself produced hyperalgesia in the contralateral hindpaw. The results give support for a contribution of both C-fiber neuropeptides and EAAs to central nervous system plasticity and secondary hyperalgesia following heat injury.
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PMID:Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids. 168 78

The membrane lipid phase may be an important mediator of the peptide-receptor interaction. In order to understand the mechanism of this interaction, it is important to know the peptide structure, not only in the hydrophobic lipid bilayer environment, but also at the bilayer surface and in solution. To investigate this problem we have measured the secondary structure of the 11-residue neuropeptide substance P (SP) and its fragments in aqueous solutions, in membrane mimetic solvents, and associated with lipid bilayers using Raman and CD spectroscopy. Raman and CD spectra of SP bound to liposomes indicate a less than 20% helix content. We interpret these results to indicate that SP contains virtually no helix when bound to negatively charged liposomes. These spectra are similar to spectra of peptides in type I and III beta-turns. SP forms between 10 and 30% (1-3 residues) helical structure in sodium dodecyl sulfate micelles and less than 10% helix in methanol and trifluoroethanol. The binding of SP to negatively charged liposomes significantly changes the structure of the lipid acyl chains, decreasing order in some cases and increasing it in others. Raman spectra of SP in water indicates that SP near 30 mM forms an ensemble of structures in water that is distinct from completely unfolded peptide and from the aggregated beta-sheet form observed in saline solutions. We conclude from our CD results that methods used to quantitate secondary structure from CD spectra of short peptides cannot be used to distinguish between very short helical segments and beta-turns.
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PMID:Secondary structure of substance P bound to liposomes in organic solvents and in solution from Raman and CD spectroscopy. 168 89


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