ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.

Peter Ericsson, Per Norlén, Maria Lundgren, Per Alm, Peter Höglund, Rolf Håkanson

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Sammanfattning

The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
Originalspråkengelska
Sidor (från-till)57-65
TidskriftPharmacology and Toxicology
Volym93
Nummer2
DOI
StatusPublished - 2003

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Pathology, (Lund) (013030000), Division of Clinical Chemistry and Pharmacology (013250300), Department of Experimental Medical Science (013210000), Drug Target Discovery (013212045), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)

Ämnesklassifikation (UKÄ)

  • Medicinska grundvetenskaper
  • Cancer och onkologi
  • Farmakologi och toxikologi
  • Läkemedelskemi

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