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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 14 (1984), S. 420-424 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (D-Pro4 D-Trp7,9,10)SP4–11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 μM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin, does not cause histamine release from rat mast cells at concentrations up to 10 μM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The binding of [3H] γ-aminobutyric acid ([3H]GABA) and [3H]muscimol has been studied in purified synaptic plasma membrane (SPM) preparations from rat brain. Scatchard analysis of specific binding (defined as that displaced by 100 μMγ-aminobutyrate) indicated that the binding of both radiolabelled ligands was best described by a two component Langmuir adsorption isotherm. The apparent KD and Bmax values for [3H]GABA at 4°C were KD1, 20 nM; KD2,165 nM; Bmax1, 0.48 pmol;Bmax2, 6.0 pmol. mg−1; for [3H]muscimol at 4°C they were: KD1, 1.75 nM; KD2, 17.5 nM; Bmaxl, 0.84 pmol. mg−1; Bmax2, 4.8 pmol.mg−1; and for [3H]muscimol at 37°C they were: KD1, 7.0 nM; Km, 60 nM; Bmax], 0.5 pmol-mg−1; Bmax2, 7.2 pmol-mg1. Under the experimental conditions used, the similar Bmilx values for [3H]GABA and [3H]muscimol binding to the SPM preparations suggests that the high- and low-affinity components for the two radiolabeled ligands are identical. The effects of the GAB A antagonist bicuculline on the binding of [3H]muscimol at 4CC and 37°C were studied. At 4°C, antagonism of muscimol binding appeared to be competitive at the high-affinity site but noncompetitive at the low-affinity site. At 37°C, antagonism was again competitive at the high-affinity site but was of a mixed competitive/noncompetitive nature at the low-affinity site. Assuming that binding to the high-affinity site is associated with the pharmacological actions of bicuculline, the apparent KD values obtained suggest a pA2 value of 5.3 against [3H]muscimol at 4°C and 37°C. This figure is in good agreement with several estimates of the potency of bicuculline based on pharmacological measurements. Results from displacement studies using [3H]GABA and [3H]muscimol suggest that [3H]GABA might be a more satisfactory ligand than [3H]muscimol in GABA radioreceptor assays.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 23 (1974), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Amino acids may be involved in primary afferent excitatory neurotransmission in the spinal cord. To test this possibility the effect of chronic dorsal root section on amino acid levels of the rabbit spinal cord has been investigated. Dorsal roots L6-S2 were sectioned under anaesthesia. Control animals were subjected to similar surgical procedures but the dorsal roots were left intact. Electromyogram recordings taken 6 days after surgery confirmed the absence of sensory input to the lower lumbosacral cord of dorsal root sectioned animals although motor function was retained. In contrast to this control animals exhibited normal reflex activity. The spinal cord was removed from each animal and extracted in trichloracetic acid for subsequent analysts of amino acids on an autoanalyser. Sections of cord were retained for histological determination of neuronal degeneration. Comparison of amino acid levels in dorsal root sectioned and control animals revealed that the only excitatory amino acid to be significantly reduced by dorsal root section wasaspartic acid (–50 percent X although glutamic acid was also reduced (– 30 per cent). Two inhibitory amino acids, cystathionine and GABA, were also significantly depleted (– 50 and - 35 per cent). The possible involvement of these amino acids in spinal cord neurotransmission is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The early histological features of indomethacin-induced jejunal injury in the rat are described in tissues preserved by perfusion-fixation with 10% formolsaline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion-fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous ‘tufting’. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper-third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one-third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID-induced jejunal injury in the rat are discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 9 (1995), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims: To examine the effects of a pepsin inhibitor, pepstatin-A, a long acting H2-receptor blocker, loxtidine, exogenous pepsin and exogenous acid against indomethacin-induced antral ulceration in the rat. Results: Indomethacin (60 mg/kg s.c.) caused antral ulceration in fasted/re-fed rats over a period of 4 h. Ulceration was prevented in a dose-dependent manner by treatment with pepstatin-A (0.1–1 mg.kg hourly) or loxtidine (3 mg/kg) given orally. Acidified methylcellulose (1 mL hourly per os) enhanced damage and also prevented protection by loxtidine (3 mg/kg per os). The protection by pepstatin-A was not altered by treatment with acidified methylcellulose but was reversed by treatment with a 10-fold excess of pepsin. Conclusion: These studies suggest that mucosal degradation by pepsin, rather than direct damage by luminal acid, was the major factor in the development of indomethacin-induced antral ulceration in the rat.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 33 (1990), S. 1848-1851 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Betahistine produced a concentration-dependent contraction of the guinea-pig ileum and was about 27 times less active than histamine in this respect. Betahistine induced desensitization of contractile responses to histamine in the guinea-pig ileum. The H1 histamine receptor antagonist mepyramine was a competitive antagonist of the action of betahistine on the guinea-pig ileum. Betahistine caused relaxation of the rat uterus contracted by acetylcholine, and this action of betahistine was blocked by the H2 receptor antagonist cimetidine. Betahistine had a concentration-dependent positive chronotropic action on isolated guinea-pig atria, and in this respect was tenfold less potent than histamine. The action of betahistine on the atria was blocked by the H2 receptor antagonist YM11170. Betahistine caused a concentration-related contraction of the isolated lung parenchymal strip of the guinea-pig, and YM11170 potentiated this effect. Betahistine failed to release histamine from rat peritoneal mast cells at concentrations up to 100 μM and it did not prevent histamine release induced by either substance P or anti-IgE. Betahistine produced a dose-related flare and wheal reaction when injected intradermally into human skin. It is concluded that betahistine has agonist activity at both H1 and H2 receptors for histamine.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurocytology 15 (1986), S. 543-543 
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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