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)

Three N-terminal fragments of the neurotransmitter Substance P as well as two antagonist heptapeptides containing D-amino-acid residues were studied using different 1D and 2D NMR techniques. Total nonexchangeable 1H-NMR assignments were carried out in D2O and the NH protons were assigned in H2O by means of COSY experiments. The spectral data indicates that there are no preferred conformations for the backbone. The N-terminal tetrapeptide SP1-4-OH exists as a mixture of cis/trans isomers and this effect was studied as a function of pH.
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PMID:An NMR study of the conformations of N-terminal substance P fragments and antagonists. 248 53

Airway responses to rapid intravenous infusions of substance P (SP), selected carboxy terminal fragments (SP3-11, SP5-11, SP7-11, and SP9-11), and an amino terminal fragment (SP1-9) were measured in anesthetized, mechanically ventilated guinea pigs. The dose of each peptide required to decrease pulmonary conductance (GL) to 50% of baseline value was calculated in each animal. The order of ED50GL was: SP5-11 less than SP3-11 less than SP less than SP7-11. SP9-11 and SP1-9 were inactive at doses up to 1000 nmol/kg i.v. The effects of the neutral metalloendopeptidase (NEP) inhibitor, thiorphan, and the angiotensin converting enzyme (ACE) inhibitor, captopril, on airway responses to SP5-11 were examined in order to test the hypothesis that differences in degradation of SP and SP5-11 contribute to the difference in airway responsiveness to the two peptides. Thiorphan (0.5 mg/animal, i.v.) caused a significant decrease in ED50GL for SP5-11, as has been previously noted for SP. In contrast, captopril (1.7 mg/animal i.v.) had no effect on ED50GL for SP5-11, although it has a substantial effect on SP responses. These results indicate that while the carboxy terminal of SP is essential for peptide bronchoactivity, loss of amino terminal peptides (up to four residues) actually enhances bronchoconstrictor responses to the peptide. Part of this enhancement appears to result from differences in the degradation of SP and SP5-11 by ACE. The data suggest that cleavage of SP by dipeptidyl aminopeptidases could enhance its bioactivity.
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PMID:Airway responses to substance P and substance P fragments in the guinea pig. 248 79

Previous studies with N-terminal fragments of substance P (SP) have suggested the existence of two separate SP receptor populations. SP1 receptors are found in guinea pig ilea and rat colons. SP2 receptors are found in mouse spinal cords and rat salivary glands. We have now found that substitution of Gly9 in substance P's C-terminal hexapeptide leads to an analog (L-Pro9 SP6-11) which selectively and potently stimulates SP2 receptors. In contrast, substitution of the same residue with D-Proline results in a potent and selective agonist for SP1 receptors. The data dramatically confirm the distinction between SP1 and SP2 receptors and demonstrate that the two receptors have distinct stereochemical architectures.
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PMID:Stereospecificity of SP1 and SP2 substance P receptors. 257 10

Explants and cell cultures of embryonic chick ganglia trigeminalia, telencephalon and retina or hippocampus from fetal rats were incubated in maximow chambers in the presence of cyclic AMP and the dipeptide cyclo(Lys-Pro).HCL under various conditions. Maintenance of nerve cells and growth of nerve fibers were observed by morphometrical methods. 1. Cyclo(Lys-Pro).HCL promoted the maintenance of neuroblasts and the growth of nerve fibres in explants of the ganglion trigeminal and retinal cell cultures. The effect depended on the presence of serum in the medium by use of poly-I-lysine substrate. 2. Extern applicated cyclic AMP and the dipeptide SP3-4 = cyclo(Lys-Pro).HCL facilitated neurite growth in PNS cultures. In the presence of the drugs the length of nerve fibers increased for a short term. On CNS explants substance P (SP1-11) and SP3-4 were without effect. Cyclic AMP stimulated the growth of nerve fibers in CNS explants and cell cultures in number and length. 3. Discussed is the effect of SP1-11 and cyclo(Lys-Pro).HCL for competence of nerve fibre regeneration in vitro in relation to increasing cAMP levels, which may then act as an initial second messenger. It is suggested that explants and cell cultures of nervous tissues will be useful as a tool for the further characterisation of factors with neuronotrophic activities.
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PMID:[Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture]. 282 94

Naloxone causes a tonic contraction (= "gut dependence") of the ileum in morphine-dependent rats. This "gut dependence" can be antagonized by morphine (2.5 X 10(-7) g/ml). Substance P-undecapeptide (SP1-11) produces a tonic contraction of the ileum in morphine-independent rats and also in morphine-dependent rats. In the latter, this tonic contraction is comparable with the naloxone-induced contraction. When morphine-dependent rats with naloxone-induced "gut dependence" are given SP1-11, they show an additional increase in tonus followed by a rapid tonus inhibition. Substance P-heptapeptide (SP5-11) also causes a naloxone-like contraction in both the morphine-dependent and the morphine-independent rats. In contrast to SP1-11, SP5-11 produces neither a tonus superposition nor a tonus inhibition in morphine-dependent rats with naloxone-induced "gut dependence". The fact that SP5-11 does not, in contrast to SP1-11, exert these two effects (tonus superposition and subsequent tonus inhibition) is indicative of differences between the mechanisms of the two Substance P sequences.
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PMID:[Differences in activity between substance P and substance P-heptapeptide as studied on the phenomenon of "gut dependence" in rats (author's transl)]. 618 Apr 43

The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.
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PMID:Use of substance P fragments to differentiate substance P receptors of different tissues. 618 Apr 59

1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 microM. 2 At concentrations in the range 2.5 to 1 0 microM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin, 2.5 to 10 microM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. 4 [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP4-11) all inhibited histamine release by substance P, but physalaemin did not. 5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin. 6 [D-Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7,9]SP1-11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.
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PMID:Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin. 618 39

The thermoregulatory effects of intraperitoneally administered substance P (SP1-11) (250 micrograms/kg), or equimolar quantities of SP1-4 and SP5-11 were studied in conscious rats at an ambient temperature of 4 degrees C. SP1-11 produced hypothermia, whereas SP1-4 and SP5-11 had no influence. The hypothermic effect of SP1-11 was partially antagonized by naloxone. Thus, an opiate-dependent step seems to be involved in the action of SP1-11.
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PMID:Effects of substance P and shorter analogs on body temperature in the rat. 618 55

Explants of the ganglion trigeminale (PNS) and of the telencephalon (CNS) from chick embryos were cultivated in MAXIMOW chambers in semisynthetic media in the presence of dipeptide fragments (Lys(Z)-Pro . HCl, Lys-Pro-2HBr, Arg-Pro-2HCl) and the heptapeptide (SP5-11) of substance P as well as the complete substance P (SP1-11). 1. Histological examination of the dipeptide-treated CNS explants indicates that the structure of outgrowth in vitro is changed. Fascicel were observed. A stimulation of nerve fibre extension did not take place. 2.1. In dipeptide-treated PNS cultures the index of areas covered by the explants increased. 2.2. The index of nerve fibre growth increased significantly. The stimulation was caused in multiplication of fibres. Only Lys(Z)-Pro . HCl presents a prolongation of neurites. 2.3. SP5-11 effects in no case the growth of nerve fibres. SP1-11 stimulated significantly the fibre regeneration. 3. The possible role of SP1-11 with different effects under in vitro conditions is discussed. Only the N-terminal dipeptides stimulate the growth of nerve fibres. The C-terminal SP5-11 is without effect. Finally it is stated that the best results in neuritic enlargement and neurogenesis can only be obtained by cultivation with SP1-11.
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PMID:[The effect of substance P (SP) and SP partial sequences on nerve fiber growth in tissue culture]. 618 4

Substance P (6.25-25 p-mole) produced dose-dependent flare and wheal responses when injected intradermally into the volar surface of the human forearm. The maximum flare response was obtained within the first 3 min of injection and declined thereafter. The wheal response reached a maximum after 12 min following the injection. Only those peptides having one or more basic residues in the N-terminal region were effective in producing a flare reaction. Eledoisin-related peptide and SP1-9 were 17 and 7 times less active than substance P respectively, whilst [D-pro2, D-phe7, D-trp9]SP1-11 was twice as active. The N-terminal tetrapeptide, SP1-4 and eledoisin were inactive in the dose range tested. Wheal-producing activity was not dependent on the presence of basic residues and the rank order of relative potencies was: physalaemin (2.0): [D-pro2, D-phe7, D-trp9]SP1-11 (1.1): SP1-11 (1.0): SP4-11 (0.4): SP1-9 (0.15): eledoisin-related peptide (0.08): eledoisin (0.06). The N-terminal tetrapeptide failed to produce a wheal response in the dose range tested. Substance P was approximately equi-active with poly-L-arginine in the production of wheal and flare and both of these agents were about 10 times more potent than histamine. Adenosine triphosphate (25-400 n-mole) produced dose-dependent wheal and flare responses and was 10,000 times less potent than substance P. Pre-treatment of the subjects with the H1 histamine antagonist, chlorpheniramine, (20 mg I.V.) reduced the wheal and flare responses to substance P. Local anaesthetic injection into the skin reduced the spread of the flare response but did not affect the development of the wheal response. Pre-treatment of the skin with capsaicin reduced the flare but not the wheal response to intradermal injection of histamine. The results are discussed in relation to the mechanism of the 'axon reflex' vasodilatation in skin. This is thought to involve mast cells in addition to substance P-containing primary afferent neurones.
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PMID:Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. 619 37


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