Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A receptor selective linear hexapeptide tachykinin analog, senktide, is shown to be highly ordered in solution. The conformational restriction is attributed to steric and electrostatic interactions produced by N-methylation of the third amino acid residue in the sequence and the negatively charged N-terminus. The structure of senktide is described as a dynamic mixture of similar conformations where the predominant one is a distorted antiparallel hydrogen bonded beta-pleated sheet. The observed senktide-receptor specificity is suggested to result from a selection of this or a closely related conformation.
 ...
PMID:Conformational behavior of the linear hexapeptide senktide: a receptor specific tachykinin analog. 247 55

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.
 ...
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

High-field nuclear magnetic resonance measurements were carried out on substance P fragments SP4-11' [pGlu5]-SP5-11 and [pGlu6]SP6-11 both at 400 and at 500 MHz. A spectral simulation was carried out on two of these peptides and the coupling constants were interpreted in terms of the conformations. The JNH-CHa coupling constants are all approximately 8 Hz, with the exception of glycine, indicating no preferred conformation for the backbone. For the amino acids other than p-Glu, a comparison of the coupling constant data suggests the same relative rotamer populations for the side chains. Proton longitudinal relaxation time data were measured for all three peptides and support the above conclusions.
 ...
PMID:The conformational analysis of substance P analogs using high-field NMR techniques. 248 46

In 16 consecutive patients with systemic mastocytosis, we prospectively evaluated a variety of gastrointestinal functions and examined how they relate to the occurrence of gastrointestinal symptoms. Nine patients had either a duodenal ulcer or duodenitis. Hypersecretion of gastric acid was present in 6 patients, and in these patients the mean basal acid output was 20.7 +/- 4.1 mEq/h (range 14-39 mEq/h). Impaired small intestinal absorption occurred in 5 patients, although this was usually mild. The mean fractional emptying rate of liquids for all patients (14.7% +/- 2.3% per minute) did not differ from that for controls (10.7% +/- 0.6% per minute). Mean mouth-to-cecum transit time measured by breath hydrogen testing was the same among patients (87.7 +/- 6.7 min) and controls (86.7 +/- 8.0 min). Plasma histamine concentrations were increased in all patients (mean 1886 pg/ml, range 480-7450) and correlated with the basal acid output (r = 0.64, p less than 0.02) but not maximal acid output or the presence or absence of pain or diarrhea. Mean fasting plasma concentrations of motilin, substance P, and neurotensin from 6 patients did not differ significantly from controls, whereas gastrin and vasoactive intestinal peptide were significantly less than in controls (p less than 0.01). Gastrointestinal symptoms, consisting of abdominal pain or diarrhea, occurred in 80% of patients. Abdominal pain classified as dyspeptic was usually associated with acid-peptic disease of the duodenum and hypersecretion of gastric acid, whereas abdominal pain of a nondyspeptic character was not. Only in those cases of diarrhea consisting of greater than 200 g stool/day was gastric acid hypersecretion frequently found. Neither fecal urgency nor nondyspeptic pain could be accounted for by alterations of gastrointestinal transit. These results demonstrate that gastrointestinal symptoms, peptic disease, and mild malabsorption are much more common than described previously in patients with systemic mastocytosis. Furthermore, the results provide no evidence for the contention that altered gastrointestinal transit is involved in the pathogenesis of these symptoms.
 ...
PMID:Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. 339 14

[1,2-(3)H(2)]Cholecalciferol has been synthesized with a specific radioactivity of 508mCi/mmol by using tristriphenylphosphinerhodium chloride, the homogeneous hydrogen catalyst. With doses of 125ng (5i.u.) of [4-(14)C,1-(3)H(2)]cholecalciferol the tissue distribution in rachitic rats of cholecalciferol and its metabolites (25-hydroxycholecalciferol and peak P material) was similar to that found in chicken with 500ng doses of the double-labelled vitamin. The only exceptions were rat kidney, with a very high concentration of vitamin D, and rat blood, with a higher proportion of peak P material, containing a substance formed from vitamin D with the loss of hydrogen from C-1. Substance P formed from [4-(14)C,1,2-(3)H(2)]cholecalciferol retained 36% of (3)H, the amount expected from its distribution between C-1 and C-2, the (3)H at C-1 being lost. 25-Hydroxycholecalciferol does not seem to have any specific intracellular localization within the intestine of rachitic chicks. The (3)H-deficient substance P was present in the intestine and bone 1h after a dose of vitamin D and 30min after 25-hydroxycholecalciferol. There was very little 25-hydroxycholecalciferol in intestine at any time-interval, but bone and blood continued to take it up over the 8h experimental period. It is suggested that the intestinal (3)H-deficient substance P originates from outside this tissue. The polar metabolite found in blood and which has retained its (3)H at C-1 is not a precursor of the intestinal (3)H-deficient substance P.
 ...
PMID:Synthesis of (1,2- 3 H 2 )cholecalciferol and metabolism of (4- 14 C,1,2- 3 H 2 )- and (4- 14 C,1- 3 H)-cholecalciferol in rachitic rats and chicks. 432 70

CD spectra of substance P (SP) and its C-terminal partial sequences have been measured in diluted aqueous solution including variation of hydrogen ion concentration. In the far u.v. region there is an overlapping of the amide CD absorption by the CD of the phenylalanine residue aromatic side chains (217-220 nm). This complex CD absorption is reduced during changes from acidic to alkaline pH, especially in those cases where a phenylalanine residue is at the N-terminus of the peptide chain. These CD changes dependent on pH are due more to charge effects on the aromatic chromophores than to substantial conformational changes. However, solvation effects on the conformational features of SP peptides caused by the deprotonation of the amino groups have to be taken into account. CD and potentiometric titrations indicate that the N-terminal alpha-amino groups of the SP peptides in general are freely accessible to the solvent. Our studies did not give any evidence of the occurrence of ordered structures of SP peptides in diluted aqueous solution.
 ...
PMID:Circular dichroism studies of substance P and its C-terminal sequences. CD spectra in aqueous solution and effects of hydrogen ion concentration. 615 38

Material exhibiting immunoreactivity for substance P in enteric nerves, obtained from the myenteric plexus of the guinea pig small intestine, and in the peripheral ends of sensory nerves of the ureter, atrium and superior mesenteric artery, was characterized by separation by high pressure liquid chromatography, and quantified by radioimmunoassay of fractions collected from the chromatograph. Capsaicin, which depletes substance P-like immunoreactivity from sensory, but not from other substance P-containing nerves, reduced the content of substance P-like immunoreactivity in ureter, atrium and superior mesenteric artery by more than 99.5%, whereas the reduction in immunoreactive material in the myenteric plexus was less than 10%. Separation of extracts of myenteric plexus, ureter and atrium on a reversed-phase column gave major peaks corresponding to authentic substance P and minor peaks that coeluted with oxidized substance P. If the extracts were oxidized with hydrogen peroxide before chromatography, all the immunoreactivity was found in the peak corresponding to oxidized substance P. In the superior mesenteric artery extracts, in addition to the components corresponding to substance P and its oxidized derivative, there was a small intermediate peak that has yet to be identified. Physalaemin, which has been suggested to be present in mammalian nerves, was not detectable in any of the extracts. It is concluded that both enteric nerves and the peripheral processes of sensory nerves which show immunoreactivity for substance P in this species contain the authentic peptide.
 ...
PMID:Characterization of substance P-like immunoreactivity in peripheral sensory nerves and enteric nerves by high pressure liquid chromatography and radioimmunoassay. 618 13

Preganglionic neurons in the lower lumbar spinal cord were labeled with horseradish peroxidase applied to the cut ends of the intermesenteric trunk in golden hamsters. A black granular reaction product was obtained in HRP-labeled cells by soaking spinal cord tissue in a cobalt chloride solution prior to treatment with diaminobenzidine (DAB) and hydrogen peroxide. Spinal cord sections containing labeled preganglionic neurons were processed with the immunoperoxidase (PAP) technique. Immunoreactive processes appeared as rust-brown beads. Concentrations of beaded processes exhibiting enkephalin-like, substance P-like (SPI) and somatostatin-like (SOMI) immunoreactivity were present around HRP-labeled preganglionic neurons in the intermediolateral cell column and in the dorsal commissural nucleus. Immunoreactivity was also present in the superficial dorsal horn, the dorsolateral funiculus and around the central canal. A prominent fiber system exhibiting SPI and SOMI extended from the ventral white matter to the ventral horn.
 ...
PMID:Leu-enkephalin, substance P, and somatostatin immunohistochemistry combined with the retrograde transport of horseradish peroxidase in sympathetic preganglionic neurons. 618 92

1. In previous work, we identified a prolonged and intense hyperaemic response of rat sciatic endoneurial vasa nervorum produced by epineurial application of capsaicin. We postulated that this response, which was blocked by substance P (SP) or calcitonin gene-related peptide (CGRP) antagonists, was a result of local release of neuropeptides on the 'feeding' epineurial vascular plexus. 2. In the present study, we evaluated factors that might influence capsaicin-induced hyperaemia of the rat sciatic endoneurium as measured by hydrogen clearance: central afferent connections, the epineurial vascular plexus, the release of histamine and administration of opiates. 3. Interruption of central afferent connections by proximal nerve section or removal of the epineurial vascular plexus did not influence baseline endoneurial perfusion. Plexus removal, but not proximal section, prevented capsaicin hyperaemia. 4. The epineurial vascular plexus was desensitized to the effect of capsaicin by prior application of capsaicin. Capsaicin hyperaemia was also prevented by: topical treatment with Spantide II ((D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nl e11) substance P) an SP antagonist, systemic pretreatment with a combination of H1 and H2 histamine receptor antagonists, systemic pretreatment with cromolyn sodium or systemic pretreatment with morphine. None of these pretreatments influenced baseline perfusion. When systemic morphine was given together with systemic naloxone, an opiate antagonist, capsaicin-induced hyperaemia was restored. 5. These findings indicate that the capsaicin hyperaemia of vasa nervorum is locally mediated, is independent of central afferent connections and is sensitive to a variety of interventions. It requires an intact epineurial plexus that 'feeds' endoneurial microvessels and the release of histamine by mast cells. Its inhibition by morphine suggests that there are local opiate receptors on epineurial perivascular peptidergic fibres.
 ...
PMID:Evidence that capsaicin hyperaemia of rat sciatic vasa nervorum is local, opiate-sensitive and involves mast cells. 750 27

The effects of capsaicin-sensitive nerve degeneration (capsaicin-treatment) on the corpus and the antrum was investigated in the absolute ethanol-induced lesion model in rats. The gastric lesion in the antrum were significantly aggravated by the capsaicin-treatment, while those in the corpus were not affected. To clarify the different susceptibility between the antrum and the corpus, the effects on gastric mucosal blood flow (GMBF), mucus secretion and levels of calcitonin gene-related peptide (CGRP) or substance P (Sub P), were investigated by the hydrogen gas clearance method, histochemical methods and immunohistochemical methods, respectively. The GMBF in the antrum was significantly decreased by the capsaicin-treatment, but that in the corpus was not. Moreover, capsaicin-treatment increased the mucus secretion in the antrum, but not in the corpus. Capsaicin-treatment significantly decreased CGRP- and Sub P-immunoreactive substances in the vascular smooth muscle in the antrum, but not in the corpus. On the 4th day after absolute ethanol, antral ulcers were observed. From the above results, it was suggested that capsaicin-treatment decreased the gastroprotective ability in the antrum to a greater extent than in the corpus and this may be caused by the decrease of GMBF through the decrease of CGRP- and Sub P-immunoreactive substances.
 ...
PMID:Involvement of CGRP, substance P and blood circulation in aggravating mechanism of absolute ethanol-induced antral lesions by capsaicin treatment in rats. 769 Apr 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>