The amino acid sequences of the receptors for various prostaglandins, thromboxane and lipoxin, which belong to the rhodopsin family, were aligned, and a phylogenetic tree was constructed to infer the evolutionary history of the arachidonic acid cascade. The obtained tree suggested that the origin of the cyclooxygenase pathway was different from that of the lipoxygenase pathway. The receptors involved in the cyclooxygenase pathway constructed an independent cluster, but the lipoxin A4 receptor, which is involved in the lipoxygenase pathway, belonged to the cluster of peptide receptors. The primitive form of the cyclooxygenase pathway had been a signal transduction system composed of prostaglandin E2 and its receptor associated with cAMP metabolism.
