Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

• Main Authors: T. S. Rao, J. L. Currie, A. F. Shaffer, P. C. Isakson
• Format: Article
• Language: English
• Published: Hindawi Limited 1993-01-01
• Series: Mediators of Inflammation
• Online Access: http://dx.doi.org/10.1155/S0962935193000493
• ISSN: 0962-9351; 1466-1861

The present investigation characterizes calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat) stimulated marked biosynthesis of 6-keto-PGF1α (6-KPA), TxB2, LTC4 and LTB4, with no detectable changes on levels of PGE2. Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o.) inhibited LTB4 biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo.