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)

Active substance P binding sites were solubilized from rat brain membranes by treatment with 0.125% sodium glycodeoxycholate and 1 M NaCl. About 50% of the binding activity in membrane-bound binding sites was recovered in the solubilized fraction after centrifugation at 105,000 g for 1 h. [3H]Substance P absorbed extensively to glass tubes and glass filters, but the absorption was greatly reduced by siliconizing glass tubes and preincubating glass filters in a solution containing poly-D-lysine and bovine serum albumin. [3H]Substance P was found to bind the solubilized receptors in a saturable fashion with a Bmax of 145 fmol/mg protein and a Kd of 4.6 nM, and these bindings were completely replaced by low concentrations of unlabeled substance P and physalaemin.
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PMID:Selective solubilization of physalaemin-type substance P binding sites from rat brain membranes by glycodeoxycholate and NaCl. 301 Nov 90

Rat brain aminopeptidase activity was solubilized from membranes by incubation with thiols. This novel procedure resulted in the release of the same two aminopeptidases (MI and MII) previously shown to be solubilized by the nonionic detergent Triton X-100. The solubilized aminopeptidases MI and MII were resolved by ion-exchange chromatography and further purified by hydroxylapatite chromatography. Aminopeptidase MI was shown to hydrolyze only the beta-naphthylamides of arginine and lysine whereas aminopeptidase MII exhibited a broad specificity with respect to amino acid beta-naphthylamides. Only aminopeptidase MII hydrolyzed Leu-enkephalin at a significant rate, indicating that this enzyme can account for the membrane-bound enkephalin aminopeptidase activity. The enkephalin-degrading aminopeptidase is potently inhibited by opioid (alpha-neo-endorphin and dynorphin) as well as nonopioid (substance P, somatostatin, and angiotensin I) peptides in the range of 0.2-2.0 microM. The regional distribution of aminopeptidases MI and MII in rat brain are rather different, with aminopeptidase MII distribution more closely paralleling the distribution of opiate receptors.
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PMID:Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. 388 43

The brain is both the source and the recipient of peptide signals. The question is: Do endogenous, blood-borne peptide molecules influence brain function? Brain regions with the tight capillaries of the blood-brain barrier (BBB) extract low but measurable amounts of labeled peptide molecules from an intracarotid bolus injection. In the rat, the extraction fractions of beta-casomorphin-5, DesGlyNH2-arginine-vasopressin, arginine-vasopressin, lysine-vasopressin, oxytocin, gonadoliberin, substance P, and beta-endorphin, studied in this laboratory, range from 0.5% (substance P) to 2.4% (arginine-vasopressin). Extraction varies little among the 15 examined brain regions. As shown for arginine-vasopressin, the extracted peptides may be bound in part to specific binding sites located on the luminal membrane of the tight endothelial cells. Transport of peptide molecules across the BBB cannot be ruled out, but it is unlikely that endogenous peptides pass the BBB in physiologically significant amounts. In contrast, in brain regions with leaky capillaries, e.g., selected circumventricular organs including the pineal gland, neurohypophysis, and choroid plexus, the peptide fraction extracted approaches that of water. Within the circumventricular organs, the peptide molecules actually reach the cellular elements of the tissue. However, no studies definitively show that peptides reach neurons in the deeper layers of the brain. On the other hand, blood-borne peptides influence the BBB permeability by altering the transport of essential substances. The effect may be mediated by specific peptide binding sites located at the luminal membrane of the endothelium. It is possible that the effect of peptides on the BBB is necessary for proper brain function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood-brain barrier and peptides. 389 53

Vasodepression was found ex vivo in the isolated perfused hind legs of rats, mice and guinea-pigs with paw inflammation using maximum pressure amplitude, EAm, pD2-value and intrinsic sensitivity (i.s.) as the test parameters of dose-response curves of vasopressor substances (noradrenaline, lys- and arg-vasopressin, angiotensin II, substance P, Na2-ATP). Vasodepression is strong in the anaphylactic and dextran paw edema, moderate in the carrageenin paw edema and adjuvant arthritis, but weak in the pertussis vaccine and kaolin paw edema. It is partly long-lasting, does not closely correlate with edema strength and can also be shown in the contralateral non-inflamed leg. Thus, a vasoreactivity depressing factor(s) must be liberated from the site of inflammation and reach the general circulation. Here, the method is described using the adjuvant arthritis as an example.
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PMID:Determination of reactivity of resistance blood vessels in the isolated perfused legs of animals with inflammation as exemplified in adjuvant arthritis. 396 85

This study describes effects of various peptides, neurotransmitters and cyclic nucleotides on brain polyphosphoinositide metabolism in vitro. The interconversion of the polyanionic inositol phospholipids was studied by incubation of a lysed crude mitochondrial/synaptosomal fraction with [gamma-32P]-ATP. The reference peptide ACTH1-24 stimulated the formation of radiolabelled phosphatidylinositol 4,5-diphosphate (TPI) and inhibited that of phosphatidic acid (PA). Substance P inhibited both TPI and PA labelling, whereas beta-endorphin inhibited that of PA without any effect on TPI. Morphine had no effect at any concentration tested, whereas high concentrations of naloxone inhibited the labelling of both PA and TPI. Naloxone did not counteract the effects of ACTH1-24. The other peptides tested (lysine 8-vasopressin and angiotensin II) were without any effect. Under the conditions used, adrenaline, noradrenaline and acetylcholine did not affect the labelling of the (poly)phosphoinositides. Both dopamine and serotonin, however, dose-dependently inhibited the formation of radiolabelled TPI and PA. Low concentrations of cAMP stimulated TPI, but higher concentrations had an overall inhibitory effect on the labelling of TPI, PA and especially phosphatidylinositol 4-phosphate (DPI). The cyclic nucleotide did not mediate or counteract the effects of ACTH, and cGMP was without any effect. These results are discussed in the light of current ideas on the mechanism of action of neuropeptides.
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PMID:Polyphosphoinositide metabolism in rat brain: effects of neuropeptides, neurotransmitters and cyclic nucleotides. 612 17

Isolated urethral preparations from rabbit and man responded to transmural electrical stimulation with contraction when the basal tension was low, and with relaxation when the preparations were contracted by noradrenaline, clonidine, 5-hydroxytryptamine and lysine vasopressin. Both contractant and relaxant responses were abolished by tetrodotoxin, suggesting that they were caused by the action of transmitters released from nerves. The electrically induced contractions in the rabbit urethra had a threshold frequency of 5 to 6 Hz and maximum was reached at 40 Hz. The responses were markedly reduced by alpha-receptor blockers suggesting that the released contraction-mediating transmitter was mainly noradrenaline. The relaxant response was immediate and rapidly reversible. It was obtained at a threshold frequency of 1 to 2 Hz and maximum was reached at 10 to 15 Hz. It was not inhibited by propranolol, indomethacin, atropine or peptides such as substance P, VIP, vasopressin or somatostatin. Prostaglandin E2, isoprenaline, adenosine-5'-triphosphate and VIP relaxed the noradrenaline contracted rabbit urethra with a time course different from that of the electrically induced relaxation. Nifedipine and "calcium free" solution decreased the noradrenaline induced contraction but did not influence the relaxant response to electrical stimulation. It is suggested that the relaxant response of the isolated noradrenaline-contracted urethra to electrical stimulation is caused by an unknown transmitter released from nerves.
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PMID:Electrically induced relaxation of the noradrenaline contracted isolated urethra from rabbit and man. 613 Nov 47

The unique specificity of Achromobacter protease I for lysine residue was investigated using synthetic and natural substrates, i.e., lysine derivatives, arginine derivatives, lysine vasopressin, substance P, ACTH and insulin. The enzyme cleaved only the -Lys-X- bonds in the above substrates. The binding affinity of alkylamines as determined by Ki was much stronger than that of the corresponding alkylguanidines.
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PMID:Studies on a new proteolytic enzyme from Achromobacter lyticus M497-1. II. specificity and inhibition studies of Achromobacter protease I. 616 93

The conformation of several naturally occurring peptide hormones and bioactive oligopeptides in phospholipid solutions was studied by circular dichroism. Phosphatidylcholine induced a partial helix in human gastrin I at neutral pH, but phosphatidylserine did not unless the five consecutive glutamic acid residues in gastrin were protonated. Reduced somatostatin with two lysines and substance P with one arginine and one lysine were partially helical in phosphatidylserine, but not phosphatidylcholine, solution. Both lipids induced a helical conformation in glucagon and its COOH-terminal fragment (19-29) probably because the helical segment is primarily located at the uncharged COOH terminus. Thus, polypeptides with a helix-forming potential can have the helical conformation only when the peptides carry no charge or charges opposite to those on the polar head of the lipid. Renin substrate, which has potentials for the beta form and beta turn, seemed to form a mixture of the two conformations in phosphatidylserine solution. Angiotensin I with a strong probability for the beta form adopted the beta form in phosphatidylserine solution and sleep peptide with no structure-forming potential remained unordered in lipid solutions. The helix usually predominated over the beta form in lipid solutions if the peptide has potentials for both conformations. This could account for the preponderance of helices in bacteriorhodopsin of the purple membrane, which according to its amino acid sequence would have favored the beta form.
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PMID:Lipid-induced ordered conformation of some peptide hormones and bioactive oligopeptides: predominance of helix over beta form. 618 2

1. When dorsal root ganglia were incubated in vitro with a range of concentrations of anisomycin, incorporation of [ 3H ]lysine into protein and synthesis of substance P(SP) were inhibited to a similar extent confirming that SP is synthesised by a conventional ribosomal mechanism. 2. Doses of anisomycin sufficient to inhibit protein synthesis in mouse CNS in vivo by greater than 95% did not cause a significant fall in the SP content of any of five brain areas, spinal cord, dorsal root ganglia or cornea over an 8 h period. 3. Electrical stimulation of the hind limbs however, produced a 25% fall in the SP content of the dorsal spinal cord of these animals. 4. These findings suggest that the turnover-time of neuronal SP is much longer than that of non-peptide neurotransmitters.
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PMID:Effects of synthesis inhibition and nervous activity on concentrations of neuronal substance P. 619 31

125I-angiotensin II (125I-AII) binding was examined in the hypothalamic-thalamic-septal-midbrain (HTSM) region of HLA-Wistar rats in the presence of CNS-active agents. Angiotensin I, II, and III and saralasin competed for 125 I-AII binding, whereas structurally unrelated peptides such as arginine and lysine vasopressin, oxytocin, LHRH, TRH, bradykinin, and substance P did not. In contrast, ACTH and neurotensin exhibited a weak, dose-dependent competition for 125 I-AII binding. The relative potencies of AII, AI, neurotensin and ACTH were 100:1:0.1:0.05, respectively. Neurotensin and ACTH competition was not additive with AII suggesting interaction at shared binding sites. Most importantly, a wide variety of other CNS active agents such as methyldopa, naloxone, catecholamines, clondidine, and reserpine, failed to inhibit 125 I-AII binding, thus further defining the specificity of the CNS AII receptor.
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PMID:The specificity of angiotensin II receptor binding in rat brain. 627 72


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