Antiproliferative effect of Histamine in the human adrenocortical carcinoma cell line H295R.

PAGOTTO, R; MONZÓN, C; MONDILLO, C; PIGNATARO, OP

Congreso; XLVI Reunión Anual de la SAIB; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Abstract: Histamine is a biogenic amine associated with heterogeneous functions carried out through the activation of four types of G protein coupled receptors. The current knowledge about this molecule points towards its ability to modulate proliferation in a wide variety of  cell types. The aim of this work was to evaluate the effect of Histamine on the proliferation of a human adrenocortical carcinoma cell line, H295R, and to elucidate the molecular mechanisms involved. Proliferation was assesed by tritiated thymidine incorporation and MTT assays, using Histamine and specific receptor agonists and antagonists. Second messengers were also measured. Here we report that Histamine inhibited proliferation in H295R cells. This effect was reproduced by specific Histamine receptor subtype 1 (HRH1) agonist and was prevented by the HRH1 antagonist. Competitive binding assay and immunofluorescence staining confirmed the presence of  HRH1 in this cell line. Histamine did not affect cyclic AMP levels, whereas IPs were significantly increased by this amine. In summary, the antiproliferative action of Histamine in the human adrenocortical cell line H295R would be mediated through the activation of the histamine receptor HRH1, leading to an increase in the intracellular IPs levels as the first step in this signalling pathway. Grants: X814- UBA, PIP5525-CONICET, PICT 05-38281 to OPP