How are prostaglandins and Leukotrienes formed?
Unlike histamine, which is a preformed and stored mediator, prostaglandins (PGs) and Leukotrienes (LTs) require active synthesis. They are formed from arachidonic acid, an omega-6 polyunsaturated free fatty acid (PUFFA), which is liberated from phospholipids in the cell membrane by cytoplasmic phospholipase A 2 . Arachidonic acid can then be metabolized by either of two enzyme pathways:
• The cyclooxygenase (COX) pathway results in PGs. The amount and type of PG made is determined by the expression levels of COX-1, COX-2, and cell-specific terminal synthase enzymes. As an example, platelets only make thromboxane A2 because platelets contain only COX-1 and thromboxane synthase.
• The lipoxygenase (LOX) pathway results in LTs and hydroxyeicosatetraenoic acids.
The synthesized PGs are exported from cells by the multidrug resistance-associated protein family of efflux transporters. Secreted PGs act on targets by binding to G-protein-coupled receptors. There are at least nine receptors mediating the various effects of PGs.