\s=b\Metabolites of arachidonic acid have important regulatory functions within several areas of concern to the otolaryngologist. Prostaglandins, composing one group, are involved in smooth-muscle contraction, regulation of renal glomerular blood flow, and in the modulation of immune and allergic responses, inflammation, fever, pain, and tumor growth. A second group, the leukotrienes, may be even more important than prostaglandins in allergy and inflammation. The elusive slow-reacting substance of anaphylaxis belongs in this group. Two other metabolites, thromboxane and prostacyclin, seem to be critical in hemostasis and the metastatic spread of tumors. (Arch Otolaryngol 1985;111:317-321) During the past ten years, research concerning prostaglandins and related substances has proceeded at a faster rate than any other branch of medical investigation. New com¬ pounds have been discovered, charac¬ terized, and pharmacologically ma¬ nipulated. The acquired information has rapidly moved from basic research into clinical usefulness.Since this new and complex area has profound relevance for virtually every area of medicine and surgery, we have conducted a brief review, focusing on the aspects that have particular appli¬ cation in our specialty.
METABOLISM AND PHYSIOLOGYThe family of prostaglandinlike compounds might be more correctly referred to as metabolites of arachi¬ donic acid, with true prostaglandins making up only one subset. The prostaglandins are manufactured in all cells, with the exception of those cells lacking microsomes (eg, mature red blood cells). Different cell types, how¬ ever, show marked variation in the amounts and ratios of the different arachidonic acid products. In general, they function as locally active hor¬ mones, with rapid hepatic and pulmo¬ nary catabolism resulting in very short systemic half-lives.1The major metabolic pathways from arachidonic acid are depicted in the Figure. For simplicity, some of the intermediates and less well-known products have been omitted. Arachi¬ donic acid is formed through the action of phospholipases on mem¬ brane phospholipids, which are derived from polyunsaturated longchain fatty acids. In particular, linoleic acid is an essential fatty acid alleg¬ edly because of its role as an arachi¬ donic acid precursor.2 Once in the microsomes, arachidonic acid metabo¬ lism proceeds either along the cyclo-oxygenase pathway or along the lipoxygenase pathway.In the first pathway, cyclo-oxyge¬ nase catalyzes two consecutive steps that lead to the formation of true prostaglandins (PGs). The classes of the prostaglandins are designated by letter suffixes, ie, PGE, PGD, PGF. The degree of unsaturation in a given PG is then depicted by a numerical subscript, as in PGE^PGE2, and PGF2. The important cyclo-oxygenase activity first converts arachidonic acid and molecular oxygen to the cyclic endoperoxide PGG2 and subse¬ quently to PGH2 by hydroperoxidation.3 Then PGH2 can be metabolized to any of the more stable prostaglan¬ dins (PGE2, PGD2, or PGF2), thromboxane, or to prost...
