Prostaglandins and Thromboxanes

Abstract

Prostaglandins and thromboxanes are 20-carbon-atom-chain fatty acids which contain a cyclopentane or oxane nucleus respectively. They belong to a family of icosanoids whose main intracellular precursor is arachidonic acid. These icosanoids are synthetized in all tissues (except red cells). Enzymatic hydrolysis of the arachidonic acid of lipids is the first step of their biosynthesis. This step, which is limitative, is usually catalyzed by phospholipase A2 and may be indirectly inhibited by glucocorticoids. Once released, arachidonic acid is promptly transformed into an endoperoxide intermediary through the action of an enzymatic complex called "cyclooxygenase". This intermediary is the precursor of both prostaglandins and thromboxane. Non-steroidal antiinflammatory agents such as acetylsalicylic acid and indomethacin have an inhibitory action on cyclooxygenase. The mechanisms of action of prostaglandins and thromboxane are still poorly understood. In certain tissues (platelets, adipose cells) their effect seems to involve stimulation of adenyl-cyclase and/or guanyl-cyclase. In other tissues (smooth muscle) their biological action is associated with changes in transcellular flows of calcium. Prostaglandins and thromboxane have many biological properties. Their effects are local, as they are produced in small quantities and promptly metabolized. They act more often as cell function modulators than as essential mediators. The often conflicting biological actions of these icosanoids involve: a) smooth muscles (stimulation or relaxation of blood vessel, respiratory tract, digestive tract and genitourinary tract musculatures); b) platelets (induction or inhibition of aggregation); c) the inflammatory reaction; d) the cellular fluid and electrolyte transports; e) and certain metabolic functions (lipolysis, insulin release, renin release, mobilization of bone calcium...). The advances achieved over the last decade now provide some insight into the significance of the physiologic role of icosanoids. Several prostaglandins, as well as some of their analogues, are already being used as therapeutic agents. In the future, rational manipulation of dietary fatty acids and development of selective inhibitors can be expected to provide the necessary tools for better controlling the icosanoid system in medicine.