Catecholamines Inhibit Gastric Epithelial [RGM-1] Cell Proliferation via Beta Adrenoceptors

Abstract

Summary: Catecholamines have been implicated in the modulation of normal cell growth, exerting inhibitory or excitatory control depending on the cell type. However, there is a dearth of information on the role of adrenergic mediators in gastric cell proliferation. In the present study, the effects of adrenaline (ADR) and noradrenaline (NOR) on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. Cell proliferation was assessed using [³H]-thymidine incorporation and cell cycle patterns were determined by DNA labeling with propidium iodide and flow cytometric quantification. The expressions of adrenoceptors in RGM-1 were determined by Western blot. ADR (0.01 – 10μM) and NOR (0.01 – 10μM) inhibited the growth of RGM-1 cells in a concentration-dependent manner. Pre-treatment of cells with ADR and NOR also inhibited the proliferation stimulated by epidermal growth factor (EGF). Neither phentolamine (non-selective α-adrenergic blocker), methoxamine (α1-selective agonist) nor clonidine (α2-selective agonist) significantly affected the inhibition of cell proliferation produced by ADR and NOR. Propranolol (non-selective β-adrenergic blocker) and butoxamine (selective β2-adrenergic blocker) significantly (but not totally) reversed the inhibitory action of ADR on cell proliferation. Furthermore, procaterol (selective beta-2 agonist) but not dobutamine (selective beta-1 agonist) had effects similar to those produced by ADR and NOR. Exposure of RGM-1 cells to both ADR and NOR caused significant inhibition of the G₁ – S cycle progression as evidenced by the higher percentage of the G₀/G₁ phase and a decreased S- phase. This effect was blocked by pre-treatment with propranolol but not phentolamine These results indicate that catecholamines inhibit the proliferation of RGM-1 cells probably partly through beta-2 receptors.

Keywords: Cathecholamines; RGM-1; Cell proliferation; cell cycle; flow cytometry, [3H]-thymidine

Nig. J. Physiol. Sci. 25(2010) 5 – 16