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Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment

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Abstract

Histamine in the rat stomach resides in enterochromaffin-like (ECL) cells and mast cells. The ECL cells are peptide-hormone-producing endocrine cells known to release histamine and chromogranin-A-derived peptides (such as pancreastatin) in response to gastrin. Ischemia (induced by clamping of the celiac artery or by gastric submucosal microinfusion of the vasoconstrictor endothelin) mobilizes large amounts of ECL-cell histamine in a burst-like manner. This report examines the ECL-cell response to ischemia and compares it with that induced by gastrin in rats. Arterial clamping (30 min) and gastric submucosal microinfusion (3 h) of endothelin, vasopressin, or adrenaline caused ischemia, manifested as a raised lactate/pyruvate ratio and mucosal damage. Whereas microinfusion of gastrin released both histamine and pancreastatin, ischemia mobilized histamine only. The mucosal concentrations of histamine and pancreastatin, the number and immunostaining intensity of the ECL cells, and the ultrastructure of the ECL cells were unchanged following ischemia. The long-term effects of ischemia and reperfusion (60–90 min) on gastric mucosa were examined in rats treated with the proton pump inhibitor omeprazole for 4 days. The activity of the ECL cells was suppressed (reflected in low histamine-forming capacity) but returned to normal within 1 week, illustrating the ability of the ECL cells to recover. We suggest that ischemia mobilizes cytosolic ECL-cell histamine without affecting the storage of histamine (and pancreastatin) in the secretory organelles and without causing lasting ECL-cell impairment.

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Acknowledgements

We are grateful to Professor Per Alm, Department of Pathology, Lund University Hospital (for providing facilities for processing tissue specimens for histology), to Professor Per-Olof Grände, Institute of Experimental Medical Sciences, Lund University (for helping us to determine lactate and pyruvate in the microdialysate samples), and to Professor Petter Hedlund and Brita Sundén-Andersson, Department of Laboratory Medicine, Lund University Hospital (for expertise and advice in relation to our work on isolated gastric arteries).

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Authors and Affiliations

  1. Unit of Cellular and Molecular Pharmacology, Department of Experimental Medical Sciences, BMC F13, Lund University, Lund, Sweden

    Maria Bernsand & Rolf Håkanson

  2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Chun-Mei Zhao, Björn Stenström & Duan Chen

  3. Unit of Clinical and Experimental Pharmacology, Department of Laboratory Medicine, University Hospital, 22185, Lund, Sweden

    Per Norlén

Authors
  1. Maria Bernsand
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  2. Chun-Mei Zhao
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  3. Rolf Håkanson
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  4. Björn Stenström
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  5. Duan Chen
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  6. Per Norlén
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Corresponding author

Correspondence to Per Norlén.

Additional information

This study was supported by grants from A. Påhlsson’s Foundation, Magnus Bergvall’s Foundation, the Novo-Nordisk Foundation, Nio Meter Liv, the Swedish Society for Medical Science, the Crafoord Foundation, the Juhlin Foundation, the Cancer Foundation of St. Olov’s Hospital, Trondheim, Norway, and the Medical Faculty of Lund University.

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Bernsand, M., Zhao, CM., Håkanson, R. et al. Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment. Cell Tissue Res 333, 405–415 (2008). https://doi.org/10.1007/s00441-008-0648-y

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  • DOI: https://doi.org/10.1007/s00441-008-0648-y

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