Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an earlier study we have shown that local application of capsaicin directly to one sciatic nerve induces a decrease of substance P and cholecystokinin octapeptide (CCK8)-like peptide from the dorsal spinal cord using immunocytochemical analysis. Here the effect of locally applied capsaicin on seven peptides known to be present in the L4 segment was assessed by radioimmunoassay and immunocytochemistry. The peptides investigated were substance P, somatostatin and CCK8-like peptide (which are present in small diameter primary afferent fibres), neurotensin, enkephalin (which are intrinsic to the spinal cord), neurophysin (of supraspinal origin) and bombesin (whose origin is unknown). Fourteen days after a single application of 49 mM solution of capsaicin a significant depletion of substance P and somatostatin was detected. These results were confirmed by parallel immunocytochemical analysis which localised the dramatic decreases of substance P and somatostatin to lamina 1 and lamina 2. In addition a depletion of CCK8-like immunoreactivity was observed by immunocytochemistry in this area, but quantitative radioimmunoassay of CCK8-like peptide did not detect this depletion. The capsaicin-induced changes were dose-dependent and reversible. Small decreases were noted with concentrations of capsaicin as low as 0.1 mM. The changes were apparent from day 9 onwards, maximal depletion seen by day 14. By 200 days post-operatively, a recovery to normal peptide levels in the ipsilateral dorsal horn was observed. In addition, a significant depletion of cutaneous substance P was noted in the area of the skin innervated by the capsaicin-treated nerve. These changes were accompanied by a significant increase in noxious thermal response (hind paw immersion test, T = 49 degrees C, ipsilateral leg 9.11 +/- 1.3 seconds, contralateral leg: 5.1 +/- 1.3 seconds, P = less than 0.005). The peptides neurotensin, enkephalin, neurophysin and bombesin were not affected by capsaicin treatment. These findings suggest that local application of capsaicin induces an indiscriminate depletion of peptide-containing primary sensory afferent fibres which is dose-dependent, long-lasting, but reversible.
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PMID:Local application of capsaicin to one sciatic nerve of the adult rat induces a marked depletion in the peptide content of the lumbar dorsal horn. 716 30

The actions of various peptides were studied using isolated spinal cord preparation of newborn rat. Vasopressin, substance P, thyrotropin releasing hormone, bombesin, gastrin releasing peptide, oxytocin, neurotensin, cholecystokinin-octapeptide and angiotensin II produced marked depolarizing responses of motoneurons with threshold concentrations of 5 X 10(-10)--8 X 10(-9) M. After the elimination of transsynaptic action by tetrodotoxin, the actions of these peptides were depressed to various extents, the former 5 peptides producing relatively large responses. Somatostatin and enkephalin depressed the dorsal root potential and produced slight hyperpolarization of dorsal root fibers. It is suggested that many of these peptides play important roles in synaptic transmission in mammalian spinal cord.
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PMID:Actions of vasopressin, gastrin releasing peptide and other peptides on neurons on newborn rat spinal cord in vitro. 730 Dec 1

An endo-acting proline-specific oligopeptidase (prolyl oligopeptidase [POPase], EC 3.4.21.26) was purified to homogeneity from the Triton X-100 extracts of cells of Treponema denticola ATCC 35405 (a human oral spirochete) by a procedure that comprised five successive fast protein liquid chromatography steps. The POPase is a cell-associated 75- to 77-kDa protein with an isoelectric point of ca. 6.5. The enzyme hydrolyzed (optimum pH 6.5) the Pro-pNA bond in carbobenzoxy-Gly-Pro-p-nitroanilide (Z-Gly-Pro-pNA) and bonds at the carboxyl side of proline in several human bioactive peptides, such as bradykinin, substance P, neurotensin, angiotensins, oxytocin, vasopressin, and human endothelin fragment 22-38. The minimum hydrolyzable peptide size was tetrapeptide P3P2P1P'1, while the maximum substrate size was ca. 3 kDa. An imino acid residue in position P1 was absolutely necessary. The hydrolysis of Z-Gly-Pro-pNA was potently inhibited by the following, with the Ki(app) (in micromolar) in parentheses: insulin B-chain (0.7), human endothelin-1 (0.5), neuropeptide Y (1.7), substance P (32.0), T-kinin (4.0), neurotensin (5.0), and bradykinin (16.0). Chemical modification and inhibition studies suggest that the POPase is a serine endopeptidase whose activity depends on the catalytic triad of COOH ... Ser ... His but not on a metal. The amino acid sequence around the putative active-site serine is Gly-Gly-Ser-Asn-Pro-Gly. The enzyme is suggested to contain a reactive cysteinyl residue near the active site. Amino acid residues 4 to 24 of the first 24 N-terminal residues showed a homology of 71% with the POPase precursor from Flavobacterium meningosepticum and considerable homology with the Aeromonas hydrophila POPase. The ready hydrolysis of human bioactive peptides at bonds involving an imino acid residue suggests that enzymes like POPase may contribute to the chronicity of periodontal infections by participating in the peptidolytic processing of those peptides.
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PMID:An endo-acting proline-specific oligopeptidase from Treponema denticola ATCC 35405: evidence of hydrolysis of human bioactive peptides. 752 1

In order to shed some light on the neurotransmitters in the spinothalamic tract (STT), we examined, biochemically and immunohistochemically, the contents of various neurotransmitter candidates in the terminal field of the STT after cervical hemi-chordotomy (HC) and dorsal quadrant-chordotomy (dQC) in the rat. Substance P (SP), calcitonin gene-related peptide (CGRP), enkephalin, neuropeptide Y, neurotensin, oxytocin and dynorphin A were analyzed immunohistochemically. The contents of neuropeptides (SP, CGRP and cholecystokinin octapeptide) were measured by radioimmunoassay and those of amino acids (aspartic acid, glutamic acid, gamma-aminobutyric acid (GABA) and glycine) and noradrenaline were determined using high-performance liquid chromatography. Cervical hemi-chordotomy, but not dQC, caused significant decreases of the SP-like immunoreactivity in and SP content of the ventral thalamus on the ipsilateral side, compared with that on the contralateral side and of rats subjected to sham-operation. However, neither HC nor dQC resulted in any changes in the ventral thalamic contents of other putative neurotransmitters examined. These results suggest that, in rats, the STT contains SP and that SP-positive fibers run in the ventral half of the ascending spinal tract at the cervical level.
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PMID:Substance P is a possible neurotransmitter in the rat spinothalamic tract. 753 53

JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
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PMID:JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. 756 10

Several neuropeptides, including neurotensin, somatostatin, bradykinin, angiotensin II, substance P, and luteinizing hormone-releasing hormone but not vasopressin and oxytocin, were actively metabolized through proteolytic degradation by cultivated astrocytes obtained from rat cerebral cortex. Because phenanthroline was an effective degradation inhibitor, metalloproteases were responsible for neuropeptide fragmentation. Neurotensin was cleaved by astrocytes at the Pro10-Tyr11 and Arg8-Arg9 bonds, whereas somatostatin was cleaved at the Phe6-Phe7 and Thr10-Phe11 bonds. These cleavage sites have been found previously with endopeptidases 24.16 and 24.15 purified from rat brain. Addition of specific inhibitors of these proteases, the dipeptide Pro-Ile and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-4-aminobenzoate, significantly reduced the generation of the above neuropeptide fragments by astrocytes. The presence of endopeptidases 24.16 and 24.15 in homogenates of astrocytes could also be demonstrated by chromatographic separations of supernatant solubilized cell preparations. Proteolytic activity for neurotensin eluted after both gel and hydroxyapatite chromatography at the same positions as found for purified endopeptidase 24.16 or 24.15. In incubation experiments or in chromatographic separations no phosphoramidon-sensitive endopeptidase 24.11 (enkephalinase) or captopril-sensitive peptidyl dipeptidase A (angiotensin-converting enzyme) could be detected in cultivated astrocytes. Because astrocytes embrace the neuronal synapses where neuropeptides are released, we presume that the endopeptidases 24.16 and 24.15 on astrocytes are strategically located to contribute significantly to the inactivation of neurotensin, somatostatin, and other neuropeptides in the brain.
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PMID:Endopeptidases 24.16 and 24.15 are responsible for the degradation of somatostatin, neurotensin, and other neuropeptides by cultivated rat cortical astrocytes. 790 52

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

Thyrotropin-releasing hormone, oxytocin, neurotensin, calcitonin gene-related peptide and neuropeptide Y have been proposed as putative neurotransmitters in the rostral ventrolateral medulla of the rat. To investigate the modulation of the basal blood pressure by neuropeptides, we microinjected these neuropeptides into the rostral ventrolateral medulla of the rat and examined their effects on basal blood pressure. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. Thyrotropin-releasing hormone (0.01-1 ng), oxytocin (1 and 10 ng), neurotensin (0.1-10 ng), calcitonin gene-related peptide (1 and 10 ng) and neuropeptide (1 and 10 ng) produced increases in blood pressure and/or heart rate. Ganglion blockade with hexamethonium (10 mg/kg, i.v.) blocked the pressor responses to thyrotropin-releasing hormone (0.1 ng), oxytocin (10 ng) and neurotensin (10 ng), while methylatropine (1 mg/kg, i.v.) did not affect these responses. Corticotropin-releasing factor (0.1-10 ng) and atrial natriuretic peptide (1 and 10 ng) were ineffective. These findings indicate that many neuropeptides can modify basal blood pressure when injected into the rostral ventrolateral medulla. Whether these neuropeptides play a role in the blood pressure regulation within this brain region remains to be established.
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PMID:Cardiovascular effects of microinjections of thyrotropin-releasing hormone, oxytocin and other neuropeptides into the rostral ventrolateral medulla of the rat. 821 15

Current data on the influence of neuropeptides on the growth, structure and function of cells comprising the hypothalamo-pituitary-adrenal axis were presented and discussed. The action of vasopressin, oxytocin, neurotensin, bombesin, neuropeptide Y, substance P and VIP have been evaluated. The hypothesis has been introduced that in vivo effect of some neuropeptides on the structure and function of the adrenal cortex is mediated by vasopressin.
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PMID:Involvement of neuropeptides in the regulation of growth, structure and function of the adrenal cortex. 844 30

Motility of Fallopian tubes is essential for transport of ova from peritoneal cavity uterus. Numerous substances were found to affect motility of the tubes. Catecholamines cause both relaxation and contraction isolated Fallopian tubes; it depends on type of receptor they bind for. Acetylcholine, neurotensin and oxytocin stimulate motility of the tubes, while gamma-aminobutyric acid, vasoactive intestinal peptide and substance P have an inhibitory role. Numerous cytokines and their receptors were found in human oviducts; their effects on motility remain to be established. The whole sequence of events in regulation of oviducts motility is still unknown so further investigation in the field is required.
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PMID:[Neurohumoral regulation of Fallopian tube motility]. 864 53


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