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)

The three-dimensional structures of [Cys3,6,Tyr8]-, [Gly2,Cys3,6,Tyr8]- and [DCys3,Cys6]substance P, designed as conformational analogues of substance P, have been studied by 1H-NMR (500 MHz) in different solvents and by energy calculations. As previously observed for substance P and physalaemin, two tachykinins acting via the NK-1 receptor, [Cys3,6,Tyr8]substance P presents an alpha-helical structure of the 4----8 sequence in methanol. This structure is stabilized by a beta-turn III via the formation of three hydrogen bonds involving the Cys-6, Phe-7 and Tyr-8 NH groups. In contrast to substance P, two of these hydrogen bonds are still present in dimethyl sulfoxide and in water the Cys-6 NH hydrogen bond is the only one remaining, such that a beta-turn structure inside the ring can be envisaged. In close agreement with the NMR data, the energy calculations lead to three types of folding for the core of [Cys3,6,Tyr8]substance P: a beta-turn III, a less stable beta-turn I (delta E = 3 kcal), and a beta-turn II (delta E = 4.6 kcal). The structure of Gly-Leu-Met-NH2 is strongly affected by changing the hydrophobicity of the medium. The most stable calculated conformation is the helix; however, numerous unrelated structures are destabilized by about 2-3 kcal/mol. These data are analyzed and discussed in connection with the high potency of [Cys3,6,Tyr8]substance P for both the NK-1 and NK-3 binding sites; that is the internal region of tachykinins (non-homologous amino acids) might present a similar three-dimensional structure when bound to the receptors (which may be at the origin of some lack of selectivity), whereas paradoxically the selectivity may be due to the common C-terminal sequence.
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PMID:Analysis of tachykinin-binding site interactions using NMR and energy calculation data of potent cyclic analogues of substance P. 245 17

Proton magnetic resonance techniques were used to study the conformation of the synthetic tubulin fragment Ac-tubulin (430-441) amide in H2O and 80% CD3OH/20% D2O solutions, using water suppression techniques. Proton assignments are based on two-dimensional COSY experiments combined with one-dimensional spin decoupling. A comparison of the NH proton shifts between the two solvents, namely delta(CD3OH/H2O-H2O) shows a small solvent effect for the Lys1 to Val6 region of the molecule, whereas for Gly7 to Glu12 the solvent effect is much larger. The smaller effects in the region of Lys1 to Val6 may be due to some hydrogen bonding as these protons are shielded from the solvent. These conclusions are in agreement with the circular dichroism results in 80% methanol/20% water where the alpha helix is present to the extent of 30%, whereas the peptide is completely unstructured in water with some aggregation. The temperature dependence of the NH proton shifts was also carried out. In water these shifts are of the order of 7-9 X 10(-3) ppm/K indicating that most of the protons are not involved in hydrogen bonding. In CD3OH/H2O, these values range from about 4-6 X 10(-3) ppm/K, which are compatible with the presence of hydrogen bonds. Finally, binding studies were carried out between the tubulin peptide and the undecapeptide neutrotransmitter substance P. The largest shifts are for the Tyr3 NH proton of the tubulin fragment, whereas for substance P it is for the Lys3, Gln5 and Leu10 NH protons, indicating a change in conformation of both peptides on interaction.
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PMID:A proton magnetic resonance and a circular dichroism study of the solvent dependent conformation of the synthetic tubulin fragment Ac tubulin, alpha (430-441) amide and its interaction with substance-P. 248 63

Although primary neural control of airway function is through parasympathetic pathways, more recent evidence indicates that there are important adrenergic and non-adrenergic, non-cholinergic neural mechanisms that may also influence respiratory function. The parasympathetic nervous system component includes neural receptors in the airways as well as afferent and efferent pathways that travel in the vagus nerves. Afferent vagal sensory receptors mediate the response to irritant or rapidly adapting receptor activation, Hering-Breuer, and the unmyelinated "C" fibers or "J" receptor pathways. The motor component of the parasympathetic nervous system has several important functions that regulate tone in normal system has several important functions that regulate tone in normal and obstructed airways. These pathways affect the following respiratory structures: bronchial smooth muscle; the mucociliary system; the larynx; and the nose. Finally, the parasympathetic nervous system may play a role in some species in the control of breathing and in the hyperpneic responses associated with airflow obstruction. In addition to cholinergic neural mechanisms, bronchomotor tone may also be influenced by adrenergic mechanisms and non-adrenergic, non-cholinergic neural pathways. Although there is minimal innervation of the airways by the sympathetic nervous system, there is ample evidence that beta-adrenoreceptors are present on bronchial smooth muscle. Beta-receptor stimulation not only relaxes airway smooth muscle, but also inhibits mediator release from mast cells in the airways and may alter vascular permeability. Alpha-adrenoreceptors are found in human airways and stimulation of these receptors causes bronchoconstriction. Although the importance of alpha-adrenoreceptors has been questioned, recent evidence suggests that alpha stimulation may play a role in cold air- and exercise-induced asthma. Finally, non-adrenergic, non-cholinergic nerves have been shown to cause relaxation of human airways in in vivo studies. There is increasing evidence that vasoactive intestinal peptide and peptide histidine methanol are the mediators of these responses. More recently, other neuropeptides (substance P, neurokinin A, and calcitonin gene-related peptide) have been localized in nerves in airways. These cause bronchoconstriction in vitro and may be released from afferent nerve terminals by an axon reflex. Although the precise role of these substances in controlling airway tone and bronchial secretions in humans is not fully understood, they may have important modulatory effects on the neural control of airway function.
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PMID:Cholinergic and neurogenic mechanisms in obstructive airways disease. 287 14

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

A modified fluorescence assay for alpha-amylase activity is described. The method employs amylopectin anthranilate as substrate and offers the advantages of economy of time and resources over a previously described technique using the same substrate. The sample containing alpha-amylase is incubated with the substrate for 5 min at 30 degree C in a final volume of 750 microliter. The fluorescent products of the reaction are separated from the substrate by the addition of methanol, and the methanol-soluble fluorescence is measured in a fluorescence spectrometer. A highly reproducible linear relationship between fluorescence and alpha-amylase activity is obtained for enzyme activities up to 2 units. The absolute sensitivity of the assay under these conditions was estimated to be 0.02 EU (= 0.08 EU ml-1). The application of the assay method to a study of the effects of isoprenaline and substance P-like peptides on the release of alpha-amylase from rat parotid gland slices is described. The assay is particularly suitable for studies on agonists, such as substance P, which have a low ceiling effect in terms of amylase release.
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PMID:A modified amylase assay, using a fluorescent substrate, and its application to a study of the rat parotid gland in vitro. 617 29

Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2, SP) is an undecapeptide with important properties as a neurotransmitter and with other functions. No specific antagonists and no long-acting analogues of this peptide hormone are known to date. In order to reach these goals, analogues of SP have been prepared which contain potential affinity, as well as photoaffinity labeling functions, suitable for irreversible attachment to SP receptors. We report here the synthesis of SP analogues which have the Phe residues in positions 7 or 8 replaced with (4'-NO2)Phe, (4'-NH2)Phe, (4'-N2+)Phe, and (4'-N3)Phe. Some of these peptides are used for photoaffinity labeling studies using various bioassays. The synthesis of the (NO2)Phe-containing peptide was carried out on solid phase using Nle instead of Met and the Boc strategy up to residue 4; the remaining amino acids were added using an Fmoc strategy. The protected undecapetide was cleaved by ammonolysis, purified by chromatography on silica gel with chloroform/methanol and deprotected afterwards. The amino, diazonium, and azido peptides were obtained in this sequence by chemical modification of the nitro peptides. On guinea pig ileum the modified peptides in position 8 had close to maximal activity, whereas modifications in position 7 produced some reduced activity, especially the nitro modification. No diazonium peptide produced any irreversible effects on guinea pig ileum. Photoinactivation studies were carried out on strips of guniea pig trachea, but no irreversible effects have been observed, neither permanent stimulation nor permanent inactivation. The biological activities and effects are discussed in view of the molecular properties of the synthesized analogues.
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PMID:Synthesis and biological activities of photoaffinity labeling analogues of substance P. 617 52

By 1H-NMR spectroscopy it has been shown that Substance P is largely aggregated at basic and acid pH and in saline solutions. These SP polymers dissociate rapidly by addition of pyridine and acetonitrile and slowly by addition of methanol. The difficulties previously encountered in the purification of SP and SP analogs may be attributed to this aggregation and can be overcome under disaggregating conditions. As a first application of our study we propose a reliable method for obtaining SP with good yield.
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PMID:Properties of substance P aggregates. Application to the synthesis and purification of substance P. 619 89

Physalaemin (Mr = 1284) is a potent undecapeptide from the skin of South American frogs. The amino acid sequence of the COOH-terminal region of this peptide is similar to that of substance P. An antiserum specific for the NH2-terminal sequence of physalaemin enabled the quantitation and localization of physalaemin-like immunoreactivity (PSLI) in mammalian tissues. PSLI is found in acid extracts of whole trachea from rat, rabbit, and guinea pig and in the tracheal mucosal layer in the dog, cow, and pig. The concentration determined by radioimmunoassay ranged from 1 to 15 ng/g dry weight of tissue, with rat trachea containing the highest amount. Gel filtration of an extract of rabbit trachea on Bio-Gel P-4 revealed a single peak of immunoreactivity that had an approximate Mr of 1700, similar to that detected in extracts of guinea pig and rabbit stomach. In contrast to amphibian physalaemin, mammalian PSLI 1) has a higher molecular weight, 2) is resistant to alpha-chymotrypsin or trypsin digestion, 3) elutes earlier from a C18 alkylsilane resin with increasing concentrations of methanol, and 4) can be separated from physalaemin by thin-layer chromatography. These data indicate that the mammalian PSLI is different in structure from the amphibian peptide.
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PMID:A substance with immunoreactivity to the peptide physalaemin in mammalian respiratory tissue. 716 58

N1E-115 mouse neuroblastoma cells were used to study the influence of ethanol on the 5-HT- and veratridine-induced influx of 14C-guanidinium via the 5-HT3 receptor channel and the fast sodium channel, respectively. Ethanol (10-100 mM) concentration-dependently increased the 5-HT-induced 14C-guanidinium influx, leaving the basal and veratridine (100 microM)-induced influx unaffected. The increasing effect of ethanol (100 mM) was observed at all 5-HT concentrations investigated; accordingly, ethanol increased the maximum response to 5-HT. Whereas in the absence of ethanol the concentration-response curve for 5-HT was bell-shaped, this was no longer the case when ethanol (100 mM) was present in the incubation buffer; the descending branch of the concentration-response curve for 5-HT at concentrations above 300 microM was virtually no longer observed. When, in the presence of substance P (10 microM) the 5-HT-induced 14C-guanidinium influx was already enhanced, the ability of ethanol (100 mM) to increase the 5-HT-induced influx was considerably diminished (by 72%). Preincubation of N1E-115 cells with 5-HT caused a decay of the subsequent 5-HT response ("desensitization") which was dependent on the duration of preincubation; ethanol (100 mM) did not affect the rate of this decay of the 5-HT response. The 5-HT (30 microM)-induced 14C-guanidinium influx was also increased by methanol (100 mM) and n-propanol (100 mM). The rank order of the increasing effect of the n-alkanols (at 100 mM) was: methanol < ethanol < n-propanol; i.e. the degree of enhancement increased with the lipophilicity of the alcohols.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increasing effect of ethanol on 5-HT3 receptor-mediated 14C-guanidinium influx in N1E-115 neuroblastoma cells. 747 37

The recoveries of substance P (SP) and five related peptides were evaluated on different types of solid-phase extraction sorbent. Best results were obtained by use of a C18 silica gel cartridge. Marked differences of extraction yields occurred for the different peptide fragments and, in general, recovery increased with increasing hydrophobicity of the peptide when reversed-phase materials like C18 and C8 cartridges were used. This observation is indicative of a sorption-desorption mechanism by prevailing solvophobic interactions. A similar trend was found when phenylpropyl silica gel (CPhenyl), generally known as a reversed-phase adsorbent of lower hydrophobicity, was used. It was concluded that a substantial participation of analyte-matrix pi-pi interactions has to be taken into account when extraction yields are compared with corresponding values obtained by use of a C8 cartridge. With CN silica gel cartridges, marked differences in extraction yields were obtained by use of acetonitrile or methanol as the organic modifier. As an attempt to explain this observation, conformational effects were assumed for the sorption-desorption behaviour of the peptides on the polar matrix.
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PMID:Recovery of substance P and related C-terminal fragments on solid-phase extraction cartridges for subsequent high-performance liquid chromatographic separation and radioimmunoassay. 768 Oct 69


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