Microdialysis to study the Gastrin-ECL cell Axis in the conscious rat

Peter Ericsson

    Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

    291 Nedladdningar (Pure)

    Sammanfattning

    The ECL cells constitute the major endocrine cell population in the acid-producing part of the stomach. Gastrin from G cells in the antrum is the main stimulus of gastric acid secretion. Gastrin stimulates the ECL cells in the oxyntic mucosa to mobilize histamine, which in turn stimulates the parietal cells to produce hydrochloric acid. In the present study we assessed the usefulness and limitations of the technique of gastric submucosal microdialysis for the study of ECL-cell histamine mobilization in vivo. We found the microdialysis technique to be a reliable tool for the study of the ECL-cell histamine mobilization in conscious rats. Although there was an inflammatory response to the implantation of the microdialysis probe it did not seem to affect the ECL-cell histamine mobilization. In a previous microdialysis study, gastric submucosal microinfusion of endothelin and adrenaline induced massive release of histamine and caused severe local damage to the mucosa. The results of the present study indicate that ECL cells are the source of the histamine and that endothelin and adrenaline affect ECL cells in situ in an indirect manner. Also, the mobilized histamine does not contribute to the mucosal damage. Instead, the mucosal damage is caused by ischemia and acid back diffusion. We also examined whether the vagus and the sympathetic nervous system contributes to the food- and gastrin-evoked responses of ECL cells in situ. The results suggest that vagal activation does not stimulate histamine mobilization by a direct action on the ECL cells. Instead, the ECL cells operate under long-term tonic control by the vagus, and vagal denervation of the stomach leads to ECL-cell gastrin receptor desensitization. The sympathetic nervous system was of minor importance in the food-evoked histamine response. In order to study the neuronal and hormonal regulation of gastrin secretion from G cells in situ, we developed a method for antral submucosal microdialysis. From our results it seems that the vagus exerts both stimulatory and inhibitory effect on gastrin cells in the antrum, and that the antrum is dependent on an intact vagal innervation for a normal gastrin response to food intake. Also, local neurons seem to be crucial for the food-evoked gastrin mobilization, since blocking of local neurons abolished the gastrin response. In addition, when administered locally via the microdialysis probe, adrenaline, noradrenaline, isoprenaline, serotonin, carbachol and GRP were found to stimulate G-cell gastrin mobilization while somatostatin, galanin and bradykinin were found to inhibit omeprazole-induced gastrin mobilization.
    Originalspråkengelska
    KvalifikationDoktor
    Tilldelande institution
    Handledare
    • Norlén, Per, handledare
    • Håkanson, Rolf, handledare
    Tilldelningsdatum2008 sep. 18
    Förlag
    ISBN (tryckt)978-91-86059-34-7
    StatusPublished - 2008

    Bibliografisk information

    Defence details

    Date: 2008-09-18
    Time: 09:15
    Place: GK lecture hall, BMC, Sölvegatan 19, Lund, Sweden

    External reviewer(s)

    Name: Waldum, Helge L.
    Title: Professor
    Affiliation: Trondheim, Norway

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    Ämnesklassifikation (UKÄ)

    • Farmakologi och toxikologi

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