Regulation of mast cell activation: effect of a novel semisynthetic butenolide

VERA ME; MARIANI ML; CEÑAL JP; FOGAL TH; PIEZZI RS; PENISSI AB

Mendoza

Congreso; XXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2008

Sociedad de Biología de Cuyo

The present study was designed to examine the effects of a novel semisynthetic butenolide with anti-ulcer and anti-inflammatory properties (3-benzyloxymethyl-5H-furan-2-one, BMF) on mast cell activation induced by the calcium ionophore A23187. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of BMF and then challenged with the mast cell activator A23187 (9 mM). Concentration-response and kinetic studies of mast cell serotonin release evoked by A23187, evaluation of mast cell viability and morphology by light and electron microscopy, comparative studies using ketotifen, and drug stability analysis by thin layer chromatography (TLC) were performed. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of BMF to stabilize mast cells. The comparative study with ketotifen, a well known mast cell stabilizer, showed the following order of potency: BMF³ketotifen to inhibit mast cell serotonin release induced by A23187. The present study provides the first strong evidence in favour of the hypothesis that BMF inhibits A23187-induced serotonin release from peritoneal mast cells, acting thus as a mast cell stabilizer. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.