Influence of serotonin-receptor antagonism on mast cell activation during endotoxemia

Abstract Introduction: Mast cells have been implicated in the aetiology of many diseases and are particularly important in evoking leukocyte-endothelial interactions during endotoxemia. Mast cell activity can be modified by histamine. There are only little data available whether serotonin (5-HT), another amine, is involved in alterations of mast cell activity, too. The aim of the study was to investigate the effects of the 5-HT-receptor antagonists methysergide (5-HT 1/2/7 -receptor antagonist), and ketanserin (5-HT 2A -receptor antagonist) on mesenteric mast cell activation during endotoxemia. Materials and methods: In male Wistar rats, mast cell activity was determined in the mesentery using intravital microscopy. Rats were randomised in four groups of 12 animals each. Animals underwent laparotomy and the mesentery was exposed beneath an in-vivo videomicroscope. After baseline measurment endotoxemia was induced by continuous intravenous infusion of 2 mg/kg/h endotoxin (ETX group). Animals in the ETX/5-HT 1/2 -ANT group received methysergide (1 mg/kg body weight), animals in the ETX/5-HT 2A -ANT group received ketanserin (1 mg/kg body weight) additionally prior to laparotomy and to the procedure described above. Animals in saline group served as controls and received equivalent volumes of NaCl 0.9%. Activated mast cells were stained by superfusion of the mesentery with ruthenium red. Results: The relative mast cell activity to baseline value increased significantly in all groups. Values of the ETX-group versus the ETX/5-HT 1/2 -ANT group, the ETX/5-HT 2A -ANT group, and the saline group were significantly higher at 120 min. Conclusions: Serotonin receptor antagonism using the 5-HT 1/2/7 -receptor antagonist methysergide or the 5-HT 2A -receptor antagonist ketanserin reduces endotoxin-induced mast cell activation in-vivo, most probably via the 5-HT 2A -receptor subtype.