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)

In an attempt to understand the role of Ca2+ on the bioactive conformation of peptide hormones, we have examined the interaction between Ca2+ and the neuropeptide substance P. Using CD spectroscopy to monitor conformational changes caused by Ca2+ binding, we found no significant binding of the cation by substance P in water. However, a substantial conformational change occurred in the hormone on Ca2+ addition in trifluoroethanol or an 80:20 (v/v) mixture of acetonitrile and trifluoroethanol. A biphasic binding of Ca2+ was observed in these solvents with saturation at 2 cations per hormone molecule. Mg2+ caused a relatively smaller conformational change in the hormone. A peptide corresponding to residues 1-7 at the N-terminal fragment of substance P showed a weak nonsaturating binding of Ca2+ in the nonpolar solvents whereas the 7-11 C-terminal fragment peptide displayed a binding indicative of an 1:1 Ca2+/peptide complex. Ca2+ binding by the hormone and the 7-11 fragment was also monitored by changes in fluorescence of the phenylalanyl residues. The results support the conclusion drawn from the CD data about a distinct Ca2+ binding site in the C-terminal part of substance P. The Kd values obtained from fluorescence data were 160 microM for Ca2+ and 1 mM for Mg2+ binding by substance P. The hormone and the two peptide fragments were also tested for their effect on the stability of dimyristoyl lecithin vesicles. Substance P and the N-terminal fragment caused no significant leakage of either fluorescent dyes or K+ trapped in the vesicles. Nor did they cause membrane fusion as monitored by the fluorescence quenching method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of substance P and its N- and C-terminal fragments with Ca2+: implications for hormone action. 128 41

It has been reported that perinatal exposure to opiates affects mRNA synthesis, body growth and brain development in mammals, including humans. We have observed that morphine administration in drinking water during the perinatal period alters peptide development in the striatum of the rat. There is a marked increase in substance P and met-enkephalin content, the latter is maintained even at 30 days postnatally. The transient increase or earlier maturation of substance P content is correlated by a more precocious axon terminal organization as revealed by immunocytochemical staining. The increased metenkephalin content is correlated by a higher abundance of preproenkephalin A mRNA and this correlation is particularly evident at 15 days postnatally. At earlier times both northern blotting and in situ hybridization techniques fail to show any significant difference between control and morphine exposed rats, likely because the peptide content is not very different in the two groups or at least the gap is not as wide as at later times.
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PMID:Perinatal morphine exposure alters peptidergic development in the striatum. 128 3

C-fiber primary afferent sensory nerves, containing neuropeptides such as substance P and neurokinin A, mediate excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses in guinea pigs. We have studied the effects of sensory nerve depletion in vivo and at four different airway levels in vitro. Capsaicin pretreatment significantly reduced the cholinergic responses to electrical field stimulation at all airway levels studied when compared to similar responses obtained in tissues from both untreated animals and animals treated with the vehicle for capsaicin (at 8 Hz, 27.2 +/- 4.9% of maximal contraction to 10(-2) M acetylcholine in lower trachea from vehicle-pretreated animals compared with 11.6 +/- 2.9% in lower trachea from capsaicin-pretreated animals, P less than .01). Stimulation of lower tracheal segments at 30-min intervals revealed a cholinergic response which was followed by a small, delayed e-NANC component. In vivo cholinergic bronchoconstrictor responses to vagal stimulation were also significantly diminished (at 5 Hz from 11.6 +/- 2.2 cm H2O in vehicle-pretreated animals to 3.3 +/- 1.4 cm H2O in capsaicin-pretreated animals). Bronchoconstrictor responses to acetylcholine or substance P in normal, vehicle-pretreated or capsaicin-pretreated animals were not significantly different either in vitro or in vivo. Sensory neuropeptides released from C-fiber afferent nerves may facilitate cholinergic neurotransmission in airways. This effect appears more marked at airway levels in which e-NANC responses are demonstrable.
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PMID:The effect of sensory nerve depletion on cholinergic neurotransmission in guinea pig airways. 131 57

Preparation of isolated large intestine of the frog was filled with Ringer's solution diluted with distilled water (1:5) and was placed into the glass with normal Ringer's solution. The preparation was weighed within every 30 min and the osmotic permeability was determined for water of the mucous and serous layers of the intestine. Then one of the peptides was added to Ringer's solution and the experiment continued. It is stated that bombesin, neurotensin, encephalins, substance P, somatostatin, pituitrin are able to change liquid absorption from the large intestine cavity when the concentration of Ringer's solution in the cavity and from its serous surface is the same. Bombesin and neurotensin inhibited while encephalins stimulated liquid absorption and these effects depended on the transport of ions. Liquid absorption by the osmotic gradient decreased using bombesin, substance P and increased using somatostatin. More complex peptide-peptide relations are observed if using pituitrin and other peptides. cAMP is shown to participate in bombesin effects.
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PMID:[The effect of regulatory peptides on water absorption in the large intestine of the frog]. 131 80

A fluorometric, high-performance liquid chromatographic assay for transglutaminase activity is described. The method uses the small synthetic peptide benzyloxycarbonyl-L-glutaminylglycine and the fluorescent amine monodansylcadaverine as substrates. Very small amounts of substrates and enzyme are required for this assay. The reaction product is separated from substrates on a reversed-phase, C-18 column, using an isocratic elution solvent consisting of 50% methanol in water, and is detected fluorometrically with didansylcadaverine as standard. A detection limit of 31 pmol of product per injection was measured. An apparent Km of 34.7 +/- 2.4 mM was determined for the peptide substrate with purified guinea pig liver enzyme. Using this assay, a series of alkyl aldehydes was shown to inhibit transglutaminase. Modification of this assay using either gradient or isocratic elution with various proportions of acetonitrile (0.1% trifluoroacetic acid)/water (0.1% trifluoroacetic acid) afforded assays for a series of glutamine-containing peptides including substance P, alpha-endorphin, and two small, synthetic peptides. The assay is suitable for measurement of transglutaminase activity with purified enzyme or with crude preparations. This method provides a sensitive, quantitative assay for the determination of substrate and inhibitor properties of small peptides toward transglutaminases.
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PMID:A fluorometric, high-performance liquid chromatographic assay for transglutaminase activity. 135 48

The molecular characteristics of the neuropeptide substance P (SP), its agonist [Sar9,Met-(O2)11]SP, and three of its antagonists [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, [D-Arg1,D-Trp7,9,Leu11]SP, and [D-Pro2,D-Trp7,9]SP were investigated at the air/water interface and when bound to lipid monolayers and bilayers. Measurement of the Gibbs adsorption isotherm showed that the surface areas of SP and its agonist (240 +/- 5 A2 at biologically relevant concentrations) were distinctly larger than those of the antagonists (138 +/- 5 A2) [Seelig, A. (1990) Biochim. Biophys. Acta 1030, 111-118]. The surface activity of the peptides increased in the order [Sar9,Met(O2)11]SP less than SP less than [D-Pro2,D-Trp7,9]SP less than [D-Arg1,D-Trp7,9,Leu11]SP = [D-Arg1,D- Pro2,D-Trp7,9,Leu11]SP and correlated with the respective binding affinities to lipid membranes. The agonist did not insert into neutral and negatively charged bilayers or into densely packed lipid monolayers (at surface pressures greater than 31 mN/m). In contrast, the three antagonists gave rise to a strong binding both to neutral and to charged lipid monolayers and bilayers. The degree of binding was evaluated from the area increase of lipid monolayers upon peptide insertion, and the binding isotherms were analyzed in terms of the Gouy-Chapman theory. At the monolayer-bilayer equivalence pressure of approximately 32 mN/m, the binding can be described by a surface partition equilibrium with binding constants of (4.5 +/- 0.1) x 10(3) M-1 for [D-Pro2,D-Trp7,9]SP and (1.3 +/- 0.1) x 10(4) M-1 for both [D-Arg1,D-Trp7,9,Leu11]SP and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP for pure palmitoyloleoylphosphatidylcholine (POPC) membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of a substance P agonist and of substance P antagonists with lipid membranes. A thermodynamic analysis. 137 15

The localization and morphology of neurons, processes, and neuronal groups in the rat preoptic area and hypothalamus containing substance P-like immunoreactivity were studied with a highly selective antiserum raised against synthetic substance P. The antiserum was thoroughly characterized by immunoblotting; only substance P was recognized by the antiserum. Absorption of the antiserum with synthetic substance P abolished immunostaining while addition of other hypothalamic neuropeptides had no effect on the immunostaining. The specificity of the observed immunohistochemical staining pattern was further confirmed with a monoclonal substance P antiserum. The distribution of substance P immunoreactive perikarya was investigated in colchicine-treated animals, whereas the distribution of immunoreactive nerve fibers and terminals was described in brains from untreated animals. In colchicine-treated rats, immunoreactive cells were reliably detected throughout the preoptic area and the hypothalamus. In the preoptic region, labeled cells were found in the anteroventral periventricular and the anteroventral preoptic nuclei and the medial and lateral preoptic areas. Within the hypothalamus, immunoreactive cells were found in the suprachiasmatic, paraventricular, supraoptic, ventromedial, dorsomedial, supramammillary, and premammillary nuclei, the retrochiasmatic, medial hypothalamic, and lateral hypothalamic areas, and the tuber cinereum. The immunoreactive cell groups were usually continuous with adjacent cell groups. Because of the highly variable effect of the colchicine treatment, it was not possible to determine the actual number of immunoreactive cells. Mean soma size varied considerably from one cell group to another. Cells in the magnocellular subnuclei of the paraventricular and supraoptic nuclei were among the largest, with a diameter of about 25 microns, while cells in the supramammillary and suprachiasmatic nuclei were among the smallest, with a diameter of about 12 microns. Immunoreactive nerve fibers were found in all areas of the preoptic area and the hypothalamus. The morphology, size, density, and number of terminals varied considerably from region to region. Thus, some areas contained single immunoreactive fibers, while others were innervated with such a density that individual nerve fibers were hardly discernible. During the last decade, knowledge about neural organization of rodent hypothalamic areas and mammalian tachykinin biochemistry has increased substantially. In the light of these new insights, the present study gives comprehensive morphological evidence that substance P may be centrally involved in a wide variety of hypothalamic functions. Among these could be sexual behavior, pituitary hormone release, and water homeostasis.
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PMID:Distribution of substance P-immunoreactive elements in the preoptic area and the hypothalamus of the rat. 137 35

The release of substance P-like immunoreactive material (SPLI) from the vascularly perfused stomach of the rainbow trout, Oncorhynchus mykiss, was studied. In most cases, SPLI was detected in the collected vascular perfusate during experimental resting conditions. Distensions of the stomach, accomplished by a water-filled intragastric balloon, produced an initial rapid relaxation of the stomach, followed by a slow further relaxation and a stimulation of contractile activity. The amount of SPLI in the vascular perfusate was significantly elevated during the distension period. Tetrodotoxin had no effect on the response to distension or on the release of SPLI during distension, indicating release from tetrodotoxin-insensitive neurons or endocrine cells. The results suggest that a substance P-like peptide may be involved in the contractile response and/or in the maintenance of muscular tone during gastric distensions in the rainbow trout. Infusion of capsaicin had no effect on the release of SPLI. However, capsaicin caused an increase in vascular flow, an effect that could be repeated on a second infusion of capsaicin, indicating that the action may not be specific to sensory neurons.
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PMID:Release of substance P-like immunoreactive material from the stomach of the rainbow trout. 137 9

The ability of the human interleukin-1 receptor antagonist, IL-1ra, to inhibit aerosolized antigen-induced airway hyperreactivity to i.v. substance P and bronchoalveolar lavage inflammatory cell accumulation, under in vivo conditions, was assessed in guinea pigs. Pretreatment with IL-1ra (30 mg/kg i.p., administered 30 min prior to antigen challenge) inhibited increases in bronchoalveolar lavage fluid neutrophil accumulation at 1 h following aerosolized antigen (0.1% ovalbumin for 30 min) exposure. IL-1ra (30 mg/kg i.p., administered 30 min pre-antigen and 3 h post-antigen) also significantly attenuated antigen-induced increases in bronchoalveolar lavage fluid leukocytes at 6 h following antigen. However, IL-1ra (30 mg/kg i.p., administered 30 min pre-antigen as well as 6 and 12 h post-antigen) did not affect antigen-induced bronchoalveolar lavage fluid leukocyte accumulation at 24 h following antigen. A limited, but significant (P less than 0.05), reduction in antigen-induced airway hyperreactivity to 10 micrograms/kg, but not lower doses, of i.v. substance P (measured as peak increases in lung resistance in cm H2O/ml per s) at 6 h following antigen was noted in the presence of IL-1ra (30 mg/kg i.p.). In conclusion, IL-1ra inhibited antigen-induced airway hyperreactivity to i.v. substance P and bronchoalveolar lavage fluid inflammatory leukocyte influx in the guinea pig, in a time-dependent manner, suggesting that cytokines, such as IL-1, may contribute to the pathophysiology surrounding this pulmonary anaphylaxis model.
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PMID:Effect of interleukin-1 receptor antagonist on antigen-induced pulmonary responses in guinea pigs. 137 30

Substance P (SP) and calcitonin gene-related peptide (CGRP) are putative transmitters in the central and peripheral (sensory) nervous systems. In this study, we examined the effects of dependence on and withdrawal from morphine and methadone on brain SP and CGRP content. Female Long Evans rats (70-100 g) were provided with plain drinking water or solutions containing opiate. No choice of drinking fluid was allowed. The maintenance level of each opiate (0.8 and 0.4 mg/ml for morphine and methadone, respectively) was continued for 4 days. Following an injection with naloxone (10 mg/kg i.p.) or saline, animals were decapitated 0, 20, or 60 min later and regional brain peptide content was measured by specific radioimmunoassays. SP and CGRP content in opiate-maintained and naive animals were similar following saline injection. However, following naloxone injection in morphine-maintained animals, SP content was elevated in the hypothalamus and midbrain at 20 min, but by 60 min was no longer distinguishable from basal (0 min) level. CGRP content was increased in the medulla oblongata and followed a comparable time course but, unlike SP, was not altered in the hypothalamus or midbrain. No alterations were observed in methadone-maintained animals. These results correlated with the peak of the behavioral morphine withdrawal syndrome and were consistent with the comparatively milder abstinence encountered in methadone medication.
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PMID:Sub-chronic exposure to opiates in the rat: effects on brain levels of substance P and calcitonin gene-related peptide during dependence and withdrawal. 138 37


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