Figure: eicosanoid cascade

Introduction

The eicosanoid cascade is ubiquitous, occurring in virtually all tissues & body fluids. Initiation occurs in response to diverse stimuli (including response to injury) with production of a broad spectrum of biological effects. The effects include inflammation, smooth muscle contraction, hemostasis, thrombosis, parturition & gastrointestinal secretion. Products of the eicosanoid cascade are autocoids, bioagents that exert their effects locally.

Initiation of the eicosanoid cascade is facilitated by activation of phospholipase (PLC* or PLA2)with release of unsaturated fatty acid (eicosatrienoate, arachidonate, eicosapentaenoate or docosahexaenoate). These unsaturated fatty acids serve as substrates for enzymes of the cyclooxygenase cascade & lipoxygenase cascade.

* Action of phospholipase C results in formation of diacylglycerol. Subsequent & sequential action of diglyceride lipase & monoglyceride lipase release unsaturated fatty acid.

Activation of phospholipase C or phospholipase A2 may occur through release of G-proteins via activation of plasma membrane serpentine receptor or through increases in cytosolic Ca+2 concentration. Cytosolic Ca+2 increases may result via influx of Ca+ through Ca+2 channels or perturbation of the cell membrane.