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)

Formation of experimental neurosis in rats was accompanied in 64% of animals by development of amnesia of conditioned reaction of passive avoidance. Disturbance of mnestic processes was manifested by a change in free amino acids pool including the acids with neurotransmitter properties (GABA, glutamate, glycine). An increase of GABA and glycine content was found in the frontal cortex and an increase of glutamate and GABA--in the hippocampus and striate body. Substance P (125 mkg/kg) administered intraperitoneally against the background of a developed neurosis, produced in 80% of cases an antiamnestic action, accompanied by a statistically significant decrease of GABA content in the frontal cortex, hippocampus and midbrain, and an increase of glutamate in the midbrain. The level of taurine decreased in the frontal cortex, hippocampus and striate body, and increased in the midbrain. Threonine content increased in the striate body and midbrain; there was an increase of taurine, serine and glycine in the midbrain and of glycine in the striate body.
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PMID:[Effect of substance P on the reproduction of memory engrams and on the amino acid composition of brain structures in rats with experimental neurosis]. 246 61

The neurokinin A-like immunoreactivity in an extract of rabbit small intestine was resolved into two molecular forms by gel permeation chromatography. These components were purified to apparent homogeneity by reverse-phase HPLC. The primary structure of the larger component was established as the following: Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser-Phe-Val- Gly-Leu - Met.NH2. This amino acid sequence represents residues (72-92) of gamma-preprotachykinin, as predicted from the nucleotide sequence of a cloned cDNA from the rat. The peptide, termed neuropeptide-gamma, lacks residues (3-17) of neuropeptide K, and this segment is specified exactly by exon 4 in the preprotachykinin gene. The smaller form of neurokinin A-like immunoreactivity was identical to neurokinin A. Neuropeptide K was not present in the extract, demonstrating that the pathways of post-translational processing of beta- and gamma-preprotachykinins in the rabbit gut are different.
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PMID:Neuropeptide-gamma: a peptide isolated from rabbit intestine that is derived from gamma-preprotachykinin. 283 12

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.
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PMID:Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response. 290 80

We have purified angiotensin-converting enzyme (ACE, EC 3.4.15.1) from rat brain corpus striatum and rat lung. The brain enzyme has Mr 165,000 by sodium dodecyl sulfate gel electrophoresis, whereas the lung enzyme is 175,000. This difference is not an artifact of preparation since mixture of the two tissues prior to purification results in isolation of two proteins with Mr 165,000 and 175,000. Separation of tryptic fragments of 125I-labeled lung and brain ACE by reverse-phase chromatography yields distinct but similar patterns. No differences between the native enzymes are detected in dansyl-tripeptide cleavage specificity, inhibitor profile, immunological properties, sucrose gradient sedimentation, or gel filtration of ACE from the two tissues. However, lung and brain ACE can be differentiated in their ability to cleave amidated peptides. Both lung and brain ACE cleave Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (substance P) via two pathways. In one pathway, ACE first releases Gly-Leu-Met-NH2 and then dipeptides sequentially from the carboxyl terminus. The other first produces Leu-Met-NH2, and then releases dipeptides to leave substance P 1-5. Lung ACE favors initial tripeptide release 3:1, while the striatal enzyme acts via the two pathways to a similar extent. Lung and striatal ACE also differ in their ability to degrade other amidated peptides. His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 (substance K) and bombesin are degraded by striatal but not lung ACE. Physalaemin and luteinizing hormone-releasing hormone are cleaved by both enzymes, while eledoisin, kassinin, thyrotropin-releasing hormone, and substance P 5-11 are not cleaved by either enzyme. Physalaemin is degraded more rapidly by the lung enzyme. The coincidence of an ACE isozyme with substance P and substance K in the descending striatonigral pathway and the unique ability of this isozyme to cleave substance P and substance K suggest that one or both of these peptides is a physiological substrate for striatonigral ACE.
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PMID:A rat brain isozyme of angiotensin-converting enzyme. Unique specificity for amidated peptide substrates. 299 Dec 65

A novel mammalian tachykinin, designated "neuromedin L", has been isolated from porcine spinal cord by using bioassay for a tachykinin-like effect on contractility of smooth muscle preparation from guinea pig ileum. By microsequencing, the peptide has been determined to be His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2. This structure has been confirmed by synthesis. Neuromedin L is found to elicit a prompt stimulant activity on guinea pig ileum in a manner similar to that of substance P, and to have remarkable sequence homology to kassinin as well as neuromedin K, which we have recently identified as a mammalian tachykinin. These facts suggest that neuromedin L may participate in neural transmission in the same manner as other members of the mammalian tachykinin family, such as substance P and neuromedin K.
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PMID:Neuromedin L: a novel mammalian tachykinin identified in porcine spinal cord. 614 73

Receptor activation and agonist-induced desensitization of the human neurokinin-2 (NK2) receptor expressed in Xenopus oocytes have been investigated. When neurokinin A (NKA) was applied repeatedly at 5-min intervals, the second and subsequent applications gave no responses. This desensitization was not observed with the specific agonists (Lys3, Gly8-R-gamma-lactam-Leu9)NKA(3-10) (GR64349) or (Nle10)-NKA(4-10). However, in the presence of the protein kinase inhibitor staurosporine, stimulation with GR64349 or (Nle10)-NKA(4-10) induced receptor desensitization. In contrast, the protein kinase C inhibitor Ro-31-8220 was not able to enhance GR64349-mediated desensitization. We created a mutation (F248S) in the third cytoplasmic loop of NK2 that impairs NKA-induced desensitization. In the presence of either staurosporine or Ro-31-8220, the mutant receptor was desensitized in response to NKA application but not to GR64349. Also, truncation mutants delta 62 and delta 87, lacking serine and threonine residues in the cytoplasmic COOH-terminal tail, were functionally active and were partially resistant to desensitization. These observations indicate that 1) there are different conformational requirements for NK2 receptor signalling and agonist-induced desensitization, 2) the third intracellular loop and the cytoplasmic tail of NK2 are functional domains important for agonist-induced desensitization, and 3) some agonists at the NK2 receptor cause much more desensitization than others and suggest that this might result from phosphorylation by receptor-specific kinases and other non-identified protein kinases.
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PMID:A single mutation of the neurokinin-2 (NK2) receptor prevents agonist-induced desensitization. Divergent conformational requirements for NK2 receptor signaling and agonist-induced desensitization in Xenopus oocytes. 749 23

The interrelationship between somatostatin and its synthetic analog, sandostatin, with neuropeptides and inflammatory mediators, as well as their protection of gastric mucosal damage, were tested in rats. Rats were treated intragastrically with 1.0 ml of 96% ethanol with or without intravenous or intraperitoneal coadministration of somatostatin (1.0 microM/kg). Mucosal damage was also induced by the administration of either indomethacin (30 mg/kg subcutaneously) with or without intravenous sandostatin (10 micrograms/rat), given 30 min prior to damage induction. Somatostatin levels in ethanol-damaged gastric mucosa were significantly lower than in control rats. Substance P and vasoactive intestinal peptide (VIP) levels were significantly higher in the damaged mucosa in rats treated with ethanol, as was the mucosal generation of leukotriene B4 (LTB4) and cysteinyl-containing leukotrienes. The coadministration of somatostatin with ethanol significantly reduced gastric mucosal injury induced by ethanol alone. The protection of the mucosa was accompanied by reduction of mucosal substance P and VIP levels, as well as the generation of leukotrienes, an effect that was reversed by intraperitoneal or intravenous coadministration of somatostatin antagonist, cyclo-(7-aminoheptanoyl-PH-E-D-Trp-Lys-THR), 1.0 microM/100 g, with somatostatin (1.0 microM/kg) and ethanol. When given by itself somatostatin significantly reduced mucosal leukotriene generation compared with their generation in saline-treated rats. Sandostatin completely abolished gastric mucosal damage induced by indomethacin administration. In rats treated with somatostatin and indomethacin, this effect was accompanied by reduction of mucosal leukotriene generation. Administration of sandostatin to pylorus-ligated rats significantly reduced gastric acid output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin effectively prevents ethanol- and NSAID-induced gastric mucosal damage in rats. 751 Jun 7

The substance P (neurokinin-1) receptor belongs to the family of seven putative transmembrane domain receptors that are coupled via G proteins to phospholipase C activation. Homologous desensitization of substance P-stimulated responses has been described in various systems. The rat neurokinin-1 receptor and a truncated mutant lacking the carboxyl-terminal region were expressed in Chinese hamster ovary cells to examine the mechanisms of substance P-induced desensitization. Wild-type and truncated receptor-bearing cells were indistinguishable in agonist binding affinity and EC50 of substance P-induced accumulation of 3H-inositol phosphates. Substance P-induced responses continued for 30-45 min in cells expressing wild-type and truncated receptors as well as in rat LRM-55 and human U373 cells, which express endogenous neurokinin-1 receptors. In transfected cells expressing the wild-type receptor, CP-96,345 added 15 min after substance P blocked further responses, demonstrating the continuing presence of responsive receptors. The rates of accumulation of 3H-inositol phosphates were four times greater in the initial 15 s of stimulation than for the next 20 min for both wild-type and truncated receptor types. This decrease in rate of substance P-stimulated phosphatidylinositol hydrolysis is therefore not dependent on the carboxyl-terminal region of the rat neurokinin-1 receptor, which contains 26 serine and threonine residues. These results are discussed in relation to current ideas regarding neurokinin-1 receptor desensitization.
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PMID:Similar rates of phosphatidylinositol hydrolysis following activation of wild-type and truncated rat neurokinin-1 receptors. 753 7

In nucleus basalis neurons, substance P (SP) causes a slow excitation, mediated through a pertussis toxin-insensitive G protein, by suppressing an inward rectifier K+ channel. Here we report that SP applied outside the patch pipette inhibited the single-channel activity, recorded on-cell, of the inward rectifier. The PKC inhibitors staurosporine and PKC(19-36) suppressed this effect in whole-cell mode and in on-cell single-channel mode. A diacylglycerol analog mimicked the SP effect, and PKC(19-36) suppressed this analog effect. SP irreversibly suppressed the inward rectifier in neurons treated with okadaic acid. These results indicate that a diffusible messenger mediates the SP effect, that its signal transduction involves phosphorylation by PKC, and that dephosphorylation by a serine/threonine protein phosphatase mediates its recovery.
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PMID:Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons. 753 11

In order to further develop structure-activity relationships and to get information about the biological active conformations we synthetized analogues tripeptide to the FR 113680 [Ac-Thr-D-Trp(CHO)-PheNMeBzl; Ac: acethyl], in which the phenylalanine residue was replaced by unconventional amino acids [1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic); (3aS, 7aS)-octahydroindole-2-carboxylic acid (Oic); (S,S,S)-2-azabiciclo[3.3.0]octane-3-carboxylic acid (Aoc); 3-(1'-naphthyl)alanine (Nap); phenylglicine (Phg); thienylalanine (Thi)]. The biological activity of the peptides was performed on guinea pig ileum for neurokinin 1 (NK-1) and on rat colon for neurokinin 2 (NK-2). In particular, the replacement of the Phe3 by the Oic (8a) gave an higher antagonist activity in both NK-1 and NK-2 receptors, but no improvement in selectivity with respect to reference tripeptide (FR113680). The compound (8a) represent the first example of highly potent peptides that do not contain an aromatic amino acid of the third position as had been previously considered essential.
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PMID:Synthesis and biological activity of tripeptide FR113680 analogues containing unconventional amino acids. 757 38


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