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Immunoelectron microscopic study for histamine in the gastric enterochromaffin-like cells of rats treated with the proton pump inhibitor lansoprazole

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Abstract

The enterochromaffin-like (ECL) cells of the gastric mucosa in animals play an important role in gastric acid secretion. They contain few granules and numerous secretory vesicles and microvesicles. They operate under the control of circulating gastrin. In the present study, we conducted an immunoelectron microscopic study for histamine (HA) in the ECL cells of rats given the proton pump inhibitor lansoprazole (LP), which is known to induce hypergastrinemia. The pre-embedding indirect immunoperoxidase procedure utilized a mouse monoclonal antibody AHA-2 against glutaraldehyde-conjugated HA. Rats received LP (50 μg/kg per day, subcutaneously) over a period of a month, and developed hypertrophy of the ECL cells in the stomach. It was clearly demonstrated that HA was located to a much higher degree in the cytoplasm of ECL cells of LP-treated rats than in normal rats. HA immunoreactivity was observed in the cores of the granules and secretory vesicles of the ECL cells in all the rats, but in the LP-treated rats it was observed in the cores of the newly developed vacuoles as well. These results may suggest that HA may be actively generated in the cytoplasm of the hypertrophic ECL cells of LP-treated rats. Also suggested in the present study is that HA is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement, and that vacuoles are formed by the fusion of large secretory vesicles. Furthermore, the finding that relatively little HA immunoreactivity existed in the vacuoles may suggest that the vacuoles actively degrade superfluous secretory products (for example, HA) through enhanced autophagocytosis and/or oxidative stress. Another possibility may be that the membrane-bounded structure regarded as the vacuoles in this study might actually be an invagination structure produced as a result of successive series of exocytosis through which the secretory vesicles actively and rapidly release HA.

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Acknowledgements

We are grateful to Dr. Inoue of Nagasaki University for valuable suggestions throughout this study.

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Authors and Affiliations

  1. Department of Applied Life Science, Sojo University, Ikeda 4-22-1, 860-0082, Kumamoto, Japan

    Masashi Shin, Ryuichi Ueoka & Kunio Fujiwara

  2. Diagnostic Agent Development Office, Nippon Kayaku, 1-11-2 Fujimi, Chiyoda-ku, 102-8172, Tokyo, Japan

    Toshio Tanabe

  3. Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo-machi 1-14, 852-8521, Nagasaki, Japan

    Ikuo Murata, Midori Karasuyama & Kunio Fujiwara

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  1. Toshio Tanabe
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  2. Ikuo Murata
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Correspondence to Kunio Fujiwara.

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Tanabe, T., Murata, I., Karasuyama, M. et al. Immunoelectron microscopic study for histamine in the gastric enterochromaffin-like cells of rats treated with the proton pump inhibitor lansoprazole. Histochem Cell Biol 120, 401–408 (2003). https://doi.org/10.1007/s00418-003-0583-7

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