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)

1 Behavioural and biochemical effects of substance P (SP, 1 to 10 mug) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique.2 SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose-dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5-hydroxytryptamine (5-HT) turnover in the corresponding striatum.3 In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide.4 Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour.5 In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction.6 Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection.7 Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 mug), as with intracisternal SP (10 mug), evoked ;barrel rotation'.8 No changes in the free concentrations of aspartate, glutamate, gamma-aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 mug SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.
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PMID:Effects of substance P injected into the substantia nigra. 42 15

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

Neutral endopeptidase 24.11 contains an active site arginine believed to function in substrate binding. This arginine is thought to form an ionic interaction with the COOH-terminal carboxylate of NEP substrates. The functionality of arginine 102 has been investigated by using site-directed mutagenesis to produce mutants in which this residue was converted to a lysine, glycine, glutamine, or glutamate. All of the mutants exhibited essentially full activity as determined with a synthetic peptide amide, glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide. In contrast, activity was detected only with the wild-type enzyme and the lysine mutant using a synthetic substrate containing a free COOH-terminal carboxylate, dansyl-Gly-Trp-Gly. Inhibition studies with the physiologically active peptide substrates substance P, endothelin, and angiotensin I, as well as substance P free acid, [D-Ala2,Leu5]enkephalin, and [D-Ala2,Leu5]enkephalinamide indicated a lack of importance of arginine 102 in substrate binding. With [D-Ala2,Met5]enkephalin and the chemotactic peptide, N-formyl-Met-Leu-Phe, a significant decrease in affinity is observed with the arginine 102 mutants. These results suggest that the contribution of arginine 102 to substrate binding is dependent upon the strength of other subsite interactions. Examination of dipeptides as inhibitors indicates that the nature and orientation of the P'2 residue is important in determining the strength of the interaction of arginine 102 with its substrates.
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PMID:Analysis of the importance of arginine 102 in neutral endopeptidase (enkephalinase) catalysis. 137 21

The D-enantiomer of residues 2, 4, 5, 6, 7, 8, 10 and 11 was introduced in the sequence of Substance P: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH1. The achiral glycine was replaced by a D-Ala residue. The conformations of the D-substituted analogues were analysed by NMR and molecular energy calculations. Introduction of a D-amino acid in the address sequence of SP (1 to 5) distorted the helical structure of [D-Pro2]SP and [D-Pro4]SP. A D-glutamine in position 5 hampered the formation of an helix, the core of [D-Gln5]SP was stabilized by the presence of two beta-turns. The exact fitting of both Phe7 and Phe8 in the binding pocket can be achieved by either an alpha- or a 3(10) helix or two beta-turns types I and II'. Replacement of an amino acid in the message sequence, 6 to 11, drastically decreased the potencies of the corresponding analogues, different conformational modifications were observed. [D-Gln6]SP presented two beta-turns, however, the types of beta-turns should orientate the side-chains in such a way that [D-Gln6]SP did not fit in the binding site. The conformations of [D-Phe7]SP and [D-Phe8]SP were completely changed, a more or less extended structure being observed. Modifications in the Gly-Leu-Met-NH2 sequence did not affect the helical structure of the core of [D-Ala9]SP, [D-Leu10]SP and [D-Met11]SP, but decreased the percentage of extended structure of the C-terminal tripeptide.
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PMID:Influence of the replacement of amino acid by its D-enantiomer in the sequence of substance P. 2. Conformational analysis by NMR and energy calculations. 171 77

In this study we have examined the physiological and neurochemical development of the cutaneous afferent pathways from the hindlimb to the spinal cord in fetal sheep. We have shown that somatosensory input from the hindlimb evokes activity in DRG neurons at 87d gestation and in cells in the dorsal horn at 92d (term, 146d). There is evidence of immunoreactivity for substance P, calcitonin gene-related peptide and glutamine several days prior to this at 77-80 days. The implication of these findings are discussed.
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PMID:Prenatal development of cutaneous afferent connections in the spinal cord of fetal sheep. A physiological and neurochemical study. 172 44

The neuronal population of dorsal root ganglia in mouse consists of various classes of ganglion cells which may be divided in turn into subclasses by using several criteria. In class A cells, membrane-bound organelles are distributed ubiquitously throughout the large perikarya. Subclass A alpha (12%), which is characterized by large clumps of Nissl substance separated by narrow strands of neuroplasm, lacks detectable carbonic anhydrase activity. Subclass A beta (16%) displays small clusters of Nissl substance isolated by broad channels of neuroplasm and a moderate activity of carbonic anhydrase. Subclass A gamma (8%) shows the most intense carbonic anhydrase activity and a lack of uptake for [3H]L-glutamine. In class B cells (63%), the small perikarya display a zonal distribution of the organelles. Subclass B alpha contains parallel cisternae of rough endoplasmic reticulum and acid phosphatase isoenzymes present in long and curved Golgi saccules. Subclass B beta displays straight Golgi saccules rich in acid phosphatase isoenzymes and a high affinity uptake for glutamine. Subclass B gamma is characterized by the absence of acid phosphatase isoenzymes and by the presence of substance P-immunoreactivity. Class C cells (1%) have the smallest size and the highest affinity uptake for glutamine. Thus subtypes of primary sensory ganglion cells may be identified by the concomitant use of multiple criteria.
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PMID:Neuronal subpopulations in the dorsal root ganglion of the mouse as characterized by combination of ultrastructural and cytochemical features. 241 65

Porcine calpains (Ca2+-dependent cysteine proteinases) I and II, which had been purified each to a homogeneous state, were found to hydrolyze specifically carboxyl-terminal amide of substance P and several other biologically active peptidyl amides. This amidase-like activity was demonstrated both by determining released ammonia and by separating products on high-performance liquid chromatography followed by amino acid analysis. The calpain-catalyzed deamidation of substance P occurred exclusively at the carboxyl-terminal amide, leaving the side-chain glutamine intact. Enkepharinamide and MSH-release inhibiting factor were scarcely deamidated. Calpains I and II showed similar specificities for these amide substances and similar profiles of inhibitions by various protease inhibitors, but distinctly different Ca2+ requirements. The specificity constants, kcat/Km, for substance P were found to be three to four orders of magnitude higher than those for the synthetic substrates.
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PMID:Amidase-like activity of calpain I and calpain II on substance P and its related peptides. 241 62

Substance P was found to be an effective acyl donor substrate of transglutaminase in vitro, the reaction products having been examined by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fast atom bombardment mass spectrometry. Electrophoretic experiments showed that Substance P incorporated 14C-labeled polyamines when incubated with purified guinea pig liver transglutaminase and Ca2+. Extensive use of fast atom bombardment mass spectrometry allowed to establish that: i) a 1:1 adduct Substance P-spermine is formed; ii) only a single glutamine residue out of two, i.e. Gln-5, acts as acyl donor, iii) the single lysine residue of the neuropeptide is unable to act as acyl acceptor. A direct analytical methodology to detect transglutaminase reaction products is described.
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PMID:Substance P as a transglutaminase substrate: identification of the reaction products by fast atom bombardment mass spectrometry. 246 Nov 17

A new procedure for the photochemical labeling of peptides and for the production of cleavable cross-links between protein molecules is given. This method is mediated through the catalytic action of the enzyme guinea pig liver transglutaminase. Each of the labeling and cross-linking reagents described here is an amine substrate for transglutaminases and, because of the narrow specificity of these enzymes, is introduced covalently only at the gamma-carboxamide group of available peptide-bound glutamine residues. Cross-linking results either solely through the action of the enzyme in the case of a diamine substrate, or by subsequent photolysis in the case of photosensitive amine substrates. Cleavable bonds in several of the substrates are disulfide or vicinal hydroxyl groups. The validity of the procedure is demonstrated by the preparation of photosensitive derivatives of substance P and glucagon 1-6 and in the cleavable covalent cross-linking of guanidinated beta-casein.
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PMID:Transglutaminase amine substrates for photochemical labeling and cleavable cross-linking of proteins. 610 32

Effects of some possible neurotransmitters such as GABA, adrenergic drugs, and 5-HT and their antagonists on the motility of Angiostrongylus cantonensis were studied. Paralysis was caused by GABA, avermectin BIa (Av-BIa), piperazine and alpha-adrenergic agonists such as adrenaline, noradrenaline, phenylephrine, clonidine and methoxamine, but not by beta-adrenergic agonists such as isoproterenol. The paralysis by GABA or Av-BIa was antagonized by GABA antagonists such as picrotoxin and/or bicuculline with cholinergic agents such as N-methylcytisine (N-MC) or eserine. The paralysis elicited by alpha-adrenergic agonists was antagonized by alpha-adrenergic antagonists such as phentolamine and dibenamine, but not by beta-adrenergic antagonists such as propranolol. 5-HT affected the motility of A. cantonensis paralytically or spastically. The paralysis induced by 5-HT was antagonized by alpha-adrenergic antagonists such as phentolamine and dibenamine, while the contraction induced by this compound was further stimulated by N-MC, but antagonized by strychnine. Other agents such as glutamine, glycine, aspartic acid, taurine, and substance P showed little effect on the motility of A. Cantonensis. From these findings on the neuropharmacological properties of A. cantonensis, it is suggested that this worm is useful as an excellent nematodal model for the investigation of anthelminthics. In addition, this worm may also useful as one of screening models of drugs affecting the central nervous system in mammals.
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PMID:Studies on chemotherapy of parasitic helminths (VIII). Effects of some possible neurotransmitters on the motility of Angiostrongylus cantonensis. 612 26


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