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  • 5-HT3 RECEPTOR ANTAGONIST  (1)
  • ALOSETRON  (1)
  • CGRP antagonist  (1)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Digestive diseases and sciences 39 (1994), S. 1405-1408 
    ISSN: 1573-2568
    Schlagwort(e): calcitonin gene-related peptide ; CGRP antagonist ; alpha-CGRP 8-37 ; gastric acid secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The recently synthesized calcitonin gene-related peptide (CGRP) antagonist, human alpha-CGRP 8-37, was used to study its effects on gastric acid secretion. Four dogs with gastric fistula were used to measure the antagonist's physiologic effects in the stomach. All dogs received a bactopeptone dextrose meal (intragastric titration to pH 5.5) with either continuous CGRP 8-37 (1000 pmol/kg/hr) or saline (control). Additionally, intravenous bombesin (75–600 ng/kg/hr) and bethanecol (12.5–100 µg/kg/hr) was tested in the presence of the antagonist. Plasma gastrin levels also were measured via radioimmunoassay (RIA) in control and CGRP 8-37-stimulated animals. Gastric acid secretion increased by 100% with infusion of 1000 pmol/kg/hr CGRP 8-37 when compared to the control. Acid output increased 98% with both intravenous antagonist and 600 ng/kg/hr bombesin when compared to bombesin alone. However, no augmentation of acid secretion by CGRP 8-37 was shown with 25 µg/kg/hr bethanecol. RIA of plasma gastrin demonstrated no effect with the antagonist when given alone and did not increase bombesin-stimulated gastrin release. We conclude that CGRP 8-37 blocks native CGRP inhibitory effects on gastric acid secretion. Our findings of potentiation of acid secretion by bombesin as well as no change in gastrin levels in the presence of the antagonist is likely due to a blockage in a noncholinergic neuron to the somatostatin cell. Furthermore, CGRP 8-37 did not increase bethanecolstimulated acid secretion, most likely due to bethanecol's (acetylcholine) nearly ubiquitous positive effects on acid secretion.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1573-2568
    Schlagwort(e): ALOSETRON ; 5-HT3 RECEPTOR ANTAGONIST ; IRRITABLE BOWEL SYNDROME ; VISCERAL NOCICEPTION ; RECTAL DISTENSION
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Irritable bowel syndrome (IBS) represents one ofthe most common gastrointestinal-related diagnoses.Although the precise etiologic basis of IBS is notknown, a common presenting symptom is abdominal pain or discomfort that is thought to develop, atleast in part, from a heightened awareness of visceralnociceptive input. Agents capable of reducing thisheightened visceral nociception would, therefore, have utility in the treatment of IBS. In this studywe evaluated the effects of intravenous andintracerebroventricular administration of a5-HT3 receptor antagonist, alosetron, onblood pressure changes associated with rectal distension in anesthetized andawake dogs. This vasoactive reflex serves as a model forvisceral nociception. For intracerebroventricularstudies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies,blood pressure was measured by femoral arterycannulation. In awake studies, blood pressure wasmonitored by noninvasive measurement. A rectal balloonwas placed in the rectum of each dog and maintainedthroughout the experiments. Each dose of alosetron wasgiven to the dogs as an intravenous orintracerebroventricular bolus, and every 30 min therectal balloon was inflated and blood pressure responsesobserved. In both anesthetized and awake dogs alosetronproduced a significant inhibition of the vasoactivereflex. In particular, alosetron showed high potency when administered intracerebroventricularly.Alosetron, administered either centrally orperipherally, appears to modulate the visceralnociceptive effect of rectal distension indogs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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