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01 September 1998

Role of histamine H3-receptors in the proliferation of neoplastic cells in vitro

Adam Szelˆąg

Med Sci Monit 1998; 4(5): BR747-755 :: ID: 501958

Abstract

The study was devoted to the investigation of the effect of tioperamide and clobenpropit - the antagonists, as well as R-alpha-methylhistamine and imetit - the agonists of histamine H3 receptors on the proliferation of neoplastic cells in vitro. The study was performed upon the following cell lines: BM - human melanoma, A-431 - human cutaneous carcinoma, TT - human medullary thyroid carcinoma, Ta3Hauszka - mammary cancer of mice, F6B¸Y - normal bovine foetal thyroid. For each cell line, test value (TV) and test index (TI) were determined according to generally-used criteria. The study presented in our paper is the first attempt to use the modulation of histamine H3 receptors in the regulation of neoplastic cells proliferation. It was demonstrated that antagonists of histamine H3 receptors - tioperamide and clobenpropit considerably inhibit the proliferation of the cells of human neoplasms - melanoma and cutaneous carcinoma. An opposite effect was observed in the case of the agonists of these receptors - R-alpha-methylhistamine and imetit - which very clearly stimulate proliferation of these neoplastic cells. Non-neoplastic cells of normal bovine thyroid are slightly sensitive to the inhibiting activity of antagonists as well as to proliferation stimulating activity of the agonists of these receptors. The activity of the studied compounds may be associated with H3 receptors, since the antagonists of these receptors inhibit proliferating action of agonists. These observations suggest that mediators released after the use of the antagonists of these receptors, or intracellular changes taking place as an effect of their action, slow down the proliferation of neoplastic cells, but not normal cells.

Keywords: proliferation of neoplastic cells, H3 receptors

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