Ebselen inhibits contractile responses of guinea-pig parenchymal lung strips

Ebselen is a new anti-inflammatory drug with a wide spectrum of pharmacological activities. Since this compound might be useful in diseases related to airway inflammation we evaluated the effects of ebselen on the contractile responses of guinea-pig parenchymal lung strip. Ebselen and its sulfur analogue RP 62373 depressed both histamine H1-receptor-mediated and KCl-induced (50 mM) contractions of guinea-pig lung strips equipotently. The responses to histamine were only affected via depression of the maximal response; treatment with 3 microM ebselen for 30 min resulted in depression to 77 +/- 5% of the control value, whereas 10 and 30 microM inhibited the contractions to 53 +/- 4 and 52 +/- 4% of the control value respectively. The responses after membrane depolarisation (50 mM KCl) were less sensitive to ebselen pretreatment; 10 microM ebselen inhibited contractions by only 20%, whereas 30 and 100 microM depressed the response by approximately 50%. These observations were evaluated in the context of the activities of ebselen already described. The effects of lipoxygenase, cyclooxygenase, protein kinase C inhibition and thiol alkylation were studied, using established agents. However, although interaction with critical thiol groups might explain our data, the mode of action of ebselen is yet not fully elucidated.