UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to test the hypothesis that L-glutamine has differential effects on nitric oxide (NO) synthesis from L-arginine in bovine venular endothelial cells (EC) stimulated by A23187 (a Ca++ ionophore) and receptor-mediated vasodilators (bradykinin and substance P). EC were cultured at 37 degrees C for 24 h in the presence of 0.4 mM L-arginine and 0.0 to 2.0 mM L-glutamine with or without 1 microM A23187, 1 microM bradykinin or 10 microM substance P. The release of nitrite and nitrate by EC was used as an indicator of NO synthesis. A23187, bradykinin or substance P increased NO synthesis from L-arginine by EC in the presence or absence of L-glutamine. The addition of L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and L-aspartate and decreased NO synthesis by EC in a concentration-dependent manner in the presence or absence of A23187, bradykinin or substance P. L-Glutamine had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither L-glutamine nor its glutaminase metabolites (ammonia, L-glutamate and L-aspartate) had any effect on endothelial NO synthase activity. Taken together, these results suggest that the inhibition by L-glutamine of NO synthesis from L-arginine is unlikely to result from an effect of L-glutamine on L-arginine transport or NO synthase activity. Although the mechanism involved remains unknown, regulation of the arginine-NO pathway by L-glutamine may have pharmacologic and therapeutic implications in such conditions as inflammation and septic shock by inhibiting NO generation from L-arginine in endothelial cells.
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PMID:L-glutamine inhibits nitric oxide synthesis in bovine venular endothelial cells. 910 29

Rat submandibular salivary gland acinar cells were transfected by CaPO4 precipitation using a plasmid containing a replication-defective simian virus (SV40) genome. Out of 27 clonal cell lines, two were shown to have moderate to high levels of cytodifferentiation and salivary gland acinar cell function. Functional studies with the two cell lines indicated that the beta-adrenergic agonist, isoproterenol, vasoactive intestinal peptide, and prostaglandin E1 were effective activators of intracellular cyclic AMP production. Epinephrine, norepinephrine, phenylephrine, acetylcholine, and P2U-purinoceptor agonists were effective in increasing inositol phosphate production and intracellular free calcium levels, whereas substance P was without effect. Utilizing indirect immunofluorescence analysis, both cell lines were shown to express glutamine/glutamic acid-rich proteins, a submandibular acinar cell specific secretory protein family. Electron microscopic evaluation documented the maintenance of tripartite junctional complexes, cellular polarization, and the presence of moderate amounts of secretory granules and rough endoplasmic reticulum. The two cell lines had doubling times of 25 h.
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PMID:Development and characterization of SV40 immortalized rat submandibular acinar cell lines. 911 24

LC-high-resolution electrospray ionization (ESI)-MS data for a number of bioactive peptides, including substance P and bradykinins were acquired over a wide mass range by scanning the magnetic sector and calibrating externally with polyethylene glycol standards. Multiply charged ions were observed and errors between observed and theoretical monoisotopic molecular masses were typically in the 5 to 30 ppm range for the peptides during LC-ESI-MS and ESI-MS operation with magnetic sector resolutions between 2500 and 6000 (10% valley definition). Under collisionally activated dissociation conditions bn- and yn-series sequence ions were generally observed, enabling amino acid sequencing and the differentiation of lysine from glutamine, two amino acids differing in residue mass by only 0.0364 u. Mass accuracy was evaluated during an international round robin analytical exercise where the molecular masses of five unknown peptides were to be accurately determined. Isotopic clusters for charge states of up to +6 were fully resolved, facilitating the rapid and unambiguous assignment of charge states and calculation of monoisotopic molecular masses. Errors between theoretical and observed monoisotopic molecular masses were in the 2 to 18 ppm range for the five unknown peptides.
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PMID:Analysis of bioactive peptides by liquid chromatography-high-resolution electrospray mass spectrometry. 917 6

The upper esophageal sphincter (UES) is composed of the cricopharyngeus (CP), thyropharyngeus (TP; inferior pharyngeal constrictor [IPC] in humans), and cranial cervical esophagus. All 3 muscles may at times function to maintain tone in the UES, but only the CP contracts and relaxes in all physiologic states consistent with the UES. The CP is a striated muscle composed of variable-sized small (25-35 microm) muscle fibers that are primarily type I (slow twitch), highly oxidative, and contain abundant (40%) endomysial elastic connective tissue. The fibers may attach to the connective tissue framework, forming a muscular net. In humans and rats, but not other animals, the CP has no median raphe. The optimum length of the CP for development of active tension is about 1.7 times resting length; therefore, in some respects the CP acts more like cardiac than striated muscle. A passive tone in the CP is present and increases through all degrees of stretch. The high compliance of the CP allows it to be opened by distraction of other muscles (e.g., geniohyoideus) or increased intraluminal pressure. The CP is innervated by branches of the vagus nerves: pharyngoesophageal (PE), superior laryngeal (SLN), and recurrent laryngeal (RLN); glossopharyngeal (GPN); and cervical sympathetics. Only the PE and SLN provide motor fibers to the CP. The GLN may be sensory; the sympathetics may innervate the mucosa, blood vessels, and glands; but no functional innervation by the RLN has been identified. Parasympathetic ganglia and various peptides (galanin, cGRP, VIP, neuropeptide Y, substance P, tyrosine hydroxylase) have been found in the CP, but their role in control of the CP is unknown. The motoneurons of the CP are found in the nucleus ambiguus, and the innervation is ipsilateral for animal species in which the CP has a median raphe. These motoneurons are topographically organized with other pharyngeal and laryngeal muscles and the striated muscle esophagus. Pharyngeal motoneurons often have a respiratory rhythm, but not a spontaneous background discharge. Therefore, the CP motoneurons may not generate CP tone. Various reflexes control the tone of the CP. Distension of the esophagus causes contraction of the CP and UES, which is mediated by a vago-vagal reflex. Pressure on the pharyngeal mucosa contracts the CP and UES and is mediated by a glossopharyngo-vagal reflex. Inflation of the lungs causes contraction of the CP and UES, which is mediated by a vago-vagal reflex. The pharyngo-UES and pulmonary-UES reflexes may generate the respiratory rhythm often observed on UES pressure or electromyographic activity. The UES or CP also contracts with arousal or with changes in posture. All of these reflexes and responses and the passive elastic properties of the CP may contribute to the generation of tone in the CP and UES.
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PMID:Anatomy and physiology of the upper esophageal sphincter. 942 24

The ability of transglutaminase-synthesized 1,3-diaminopropane, spermidine (Spd), spermine (Spm), and monodansylcadaverine gamma-(glutamyl5)derivatives of substance P (SP) to produce bronchoconstriction was investigated. In urethane-anaesthetized guinea pigs, intravenous injections of SP derivatives contracted differently bronchial smooth muscle and caused hypotension. The most effective bronchoconstrictor among SP analogs was the gamma-(glutamyl5)Spd derivative of SP (Spd-SP; EC50 = 5.3 nmol/kg), which was more potent than the native peptide (EC50 = 26.5 nmol/kg). In contrast, the gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found completely unable to cause bronchoconstriction and was significantly less effective than SP in determining hypotension. The contractile effect of Spd-SP and Spm-SP was investigated in vitro on rat isolated colon, a well-characterized preparation rich in NK2 receptors. In addition, Spd-SP was tested on the endothelium-denuded rabbit pulmonary artery (RPA) and the hamster isolated trachea (HT), both tissue preparations containing only a single functional receptor subtype (NK2A and NK2B, respectively). The results obtained showed that Spd-SP recognizes NK2 receptors occurring on rat isolated colon more effectively (EC50 = 11 nM) than the native peptide (EC50 = 45 nM). Conversely, Spm-SP evokes a contractile response less effective than that elicited by SP (EC50 = 312 nM). Furthermore, Spd-SP (0.1-10 microg kg(-1)) produced a concentration-dependent contraction of both HT and RPA, exhibiting a potency respectively 12 and 30 times higher than SP in contracting HT and RPA. Our results indicate that the introduction of a Spd moiety at the level of glutamine-5 of SP gives rise to an analog that possesses a different capability to recognize NK2 receptors than the parent peptide. Moreover, since Spd-SP seems to contract more effectively RPA than HT, we conclude that it preferentially recognizes the NK2A receptor subtype.
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PMID:Transglutaminase-synthesized gamma-(glutamyl5) spermidine derivative of substance P is a selective tool for neurokinin-2 receptors characterization. 962 23

Substance P is an important neuromediator in spinal synaptic transmission, particularly in processing nociceptive afferent information. The effects of substance P are mediated by activation of the neurokinin 1 receptor. Evidence has suggested that excitatory amino acids such as glutamate, and prostaglandins including prostaglandin E2 are involved in the enhanced spinal excitability and hyperalgesia produced by spinal substance P. In the present study, we have demonstrated that intrathecal injection of substance P (20 nmol) in rats chronically implanted with intrathecal dialysis catheters induced a decrease in thermal paw withdrawal latency (before: 10.4+/-0.3 s; after 7.6+/-0.6 s), which was accompanied by an increase in prostaglandin E2 (362+/-37% of baseline), glutamate (267+/-84%) and taurine (279+/-57%), but not glycine, glutamine, serine or asparagine. Intrathecal injection of artificial cerebrospinal fluid had no effect upon the behavior or release. Substance P-induced thermal hyperalgesia and prostaglandin E2 release were significantly attenuated by a selective neurokinin 1 receptor antagonist RP67580, but not by an enantiomer RP68651. However, substance P-induced release of glutamate and taurine was not reduced by treatment with RP67580. SR140333, another neurokinin 1 receptor antagonist, displayed the same effects as RP67580 (i.e. block of thermal hyperalgesia and prostaglandin E2 release, but not release of amino acids). These results provide direct evidence suggesting that the spinal substance P-induced thermal hyperalgesia is mediated by an increase in spinal prostaglandin E2 via activation of the neurokinin 1 receptor. These findings define an important linkage between small afferents, sensory neurotransmitter release and spinal prostanoids in the cascade of spinally-mediated hyperalgesia. The evoked release of glutamate is apparently not a result of activation of neurokinin 1 receptors. Accordingly, consistent with other pharmacological data, acute spinal glutamate release does not contribute to the hyperalgesia induced by activation of spinal neurokinin 1 receptors.
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PMID:Intrathecal substance P-induced thermal hyperalgesia and spinal release of prostaglandin E2 and amino acids. 1007 33

The innervation pattern and the vasomotor response of the potential transmitters in the porcine pial veins were investigated morphologically and pharmacologically. The porcine pial veins were more densely innervated by vasoactive intestinal polypeptide (VIP)- and neuropeptide Y-immunoreactive (I) fibers than were calcitonin gene-related peptide (CGRP)-I, choline acetyltransferase-I, Substance P (SP)-I, and NADPH diaphorase fibers. Serotonin (5-HT)-I fibers, which were not detected in normal control pial veins, were observed in isolated pial veins after incubation with 5-HT (1 microM). 5-HT-I fibers, however, were not observed when incubation with 5-HT was performed in the presence of guanethidine (1 microM), suggesting that 5-HT was taken up into the sympathetic nerves. In vitro tissue bath studies demonstrated that porcine pial veins in the presence of active muscle tone relaxed on applications of exogenous 5-HT, CGRP, SP, VIP, and sodium nitroprusside, whereas exogenous norepinephrine and neuropeptide Y induced only constrictions. Transmural nerve stimulation (TNS) did not elicit any response in pial veins in the absence of active muscle tone. However, in the presence of active muscle tone, pial veins relaxed exclusively on TNS. This tetrodotoxin-sensitive relaxation was not affected by receptor antagonists for VIP, CGRP, 5-HT, or SP but was blocked by L-glutamine (1 mM) and abolished by Nomega-nitro-L-arginine (10 microM) and Nomega-nitro-L-arginine methyl ester (10 microM). The inhibition by L-glutamine, Nomega-nitro-L-arginine, and Nomega-nitro-L-arginine methyl ester was reversed by L-arginine and L-citrulline but not by their D-enantiomers. These results demonstrate that the vasomotor effect of all potential transmitters except 5-HT in the pial veins examined resembles that in cerebral arteries. Although porcine pial veins receive vasodilator and constrictor nerves, a lack of constriction on TNS suggests that the dilator nerves that release nitric oxide may play a predominant role in regulating porcine pial venous tone.
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PMID:Nitric oxide is the predominant mediator for neurogenic vasodilation in porcine pial veins. 1008 30

We have investigated the effect on the substrate requirements for guinea pig liver (tissue) transglutaminase of a set of 11 synthetic glutamine substitution analogues making up the full sequence of the naturally occurring tissue transglutaminase substrate substance P. While a number of peptide sequences derived from proteins that are well-recognized as tissue transglutaminase substrates have been studied, the enzyme activity using substitution analogues of full-length natural substrates has not been investigated as thoroughly. Thus, our set of substance P analogues only differs from one to other by one amino acid mutation while the length (of the peptide) is maintained as in the natural parent peptide. Our results indicate that a glutamine residue is not recognized as substrate by the enzyme whether it is placed at the N- or C-terminal or between two positively charged residues or between two proline residues. To further address the effect on enzyme activity of charged amino acids in the vicinity of the reactive glutamine residue, a new set of synthetic charge replacement analogues of substance P has been also studied. Together, the results have identified new minimal requirements for modification of a particular glutamine residue in a polypeptide chain. It would be of interest to set up a full set of such requirements in order to highlight potential glutamine residues as enzyme targets in the growing list of proteins that are being described as transglutaminase substrates.
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PMID:Addressing substrate glutamine requirements for tissue transglutaminase using substance P analogues. 1037 Nov 95

Botulinum neurotoxin B (BoNT/B) serotype specifically cleaves between the amino acids glutamine and phenylalanine (Q and F bond) in position 76-77 of synaptobrevin (VAMP2). We evaluated peptides that contain the QF cleavage site but are not identical in primary structure to the VAMP2 sequence surrounding the QF site for both inhibition of BoNT/B proteolytic activity and as substrates for BoNT/B. A reverse-phase high-performance liquid chromatography (RP-HPLC) method was used to measure digested peptides. A dose as high as 600 microM of substance P, and 11-amino acid peptide containing the QF bond, was neither a substrate nor inhibitor of BoNT/B in our assay, suggesting that more than the QF bond is required to be recognized by BoNT/B. Buforin I (B-I, QF site 24-25) is 39 amino acids in length, and sequence comparison of B-I and VAMP2 indicated a similarity of 18% for conserved amino acids around the QF site. Furthermore, computer-aided secondary structure computations predict alpha-helical structures flanking the QF site for VAMP2 and for the upstream sequence of B-I. Although predictions for the downstream sequence give nearly equal tendencies for alpha-helical and beta-sheet structures, Yi et al. showed that the downstream sequence is likely to be the alpha-helix based on their examination of buforin II (B-II, a 21-amino acid subset of B-I (16-36)), which includes the QF site and the downstream sequence of B-I. Buforin I was found not to be a substrate for BoNT/B; however, B-I dose dependently and competitively inhibited BoNT/B activity, yielding IC(50) = 1 x 10(-6) M. In contrast, B-II was not a substrate for BoNT/B and exhibited only 25% of the B-I inhibition of BoNT/B. Two additional B-I deletion peptides were tested for inhibition of BoNT/B proteolysis: peptide 36 (36 mer; containing B-I amino acids 1-36) and peptide 24 (24 mer; B-I amino acids 16-39). Peptide 24 had a similar inhibitory effect to B-II (ca. 25% of B-I) but peptide 36 was almost 50% as potent as B-I. These findings suggest that the buforin tertiary structure is important for the inhibitory activity of these peptides for BoNT/B.
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PMID:Buforin I, a natural peptide, inhibits botulinum neurotoxin B activity in vitro. 1059 94

To explore their potential use as in vivo tracers, the uptake of the amino acids glutamine, glutamate and aspartate, labeled with 11C or 14C, was evaluated in tumor cell aggregates, in vivo in rats and a few pilot studies with positron emission tomography (PET) in patients. The uptake in aggregates increased linearly with time, and was competitively inhibited by the same amino acids. The uptake of 14C-glutamate in carcinoid cells (BON) was inhibited by cystine but not by aspartate, contrary to the result in neuroblastoma (LAN). 6-Diazo-oxy-L-norleucine (a glutamine analogue) and Substance P had different effect on the uptake of glutamate in different cells. The metabolic fate of 14C-glutamate was evaluated with protein separation and with HPLC. The in vivo distribution in rats showed the highest uptake of 11C-glutamine and 11C-glutamate in pancreas and kidney, and of 11C-aspartate in the lung. In the human studies with PET, pancreas had the highest uptake followed by kidney with 11C-glutamate, and followed by spleen with 11C-aspartate. A primary pancreas tumour and metastases in liver were difficult to identify except in one case.
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PMID:Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo. 1076 63

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