THE PROSTAGLANDINS: A FAMILY OF BIOLOGICALLY ACTIVE LIPIDS

Abstract

The prostaglandins are a family of lipids, originally discovered over 30 years ago in human seminal fluid, which have since been found not only to have a wide variety of striking pharmacological actions, but also to be present in many if not all mammalian tissues. They have an unusual chemical structure, being 20-carbon fatty acids derived enzymically from the essential fatty acids by cyclization and oxidation. Converting enzymes have been demonstrated in many tissues; they are especially active in the vesicular glands of the sheep, which are used for a practical method of biosynthesis. The individual prostaglandins differ among themselves both qualitatively and quantitatively. Prostaglandins have a wide spectrum of biological action: They are smooth muscle stimulants, depressor peripheral vasodilators (except the PGFs which are pressor and venoconstrictor in dogs), and inhibitors of lipolysis, platelet aggregation and gastric secretion. In these areas, they are among the most potent compounds known, activity being present in some systems at concentrations of 0.01 ng/ml in vitro , and activity of 10 ng/kg in vivo . Prostaglandin formation and release is brought about by nerve activity, both central and peripheral. Their presence in biologically large concentrations in menstrual fluid and amniotic fluid at term is intriguing. Physiological roles for these recently rediscovered compounds are yet to be established, but whenever substances are found in tissues which in very small doses can affect the function of these tissues, there is the possibility that they are regulators of physiological activity. Each effect of one or another prostaglandin suggests a corresponding physiological role, whether stimulatory or inhibitory, on such systems as smooth muscle, nerves, the circulation, and the reproductive organs. In the last named, roles in relation to fertilityand coitus and later possible action in relation to labor and postpartum uterine contraction have been proposed. Prostaglandins liberated by nerve stimulation, which then have actions opposite to that of the nerve stimulation, suggests a role as feed-back inhibitors. Thus, sympathetic nerve stimulation to adipose tissue induces both lipolysis and the release of antilipolytic prostaglandins, and vagal stimulation to the stomach, both secretion and the release of prostaglandins with powerful antisecretory actions. On the other hand, the ability of minute amounts of certain prostaglandins, inactive in their own right, to potentiate other agonists, suggests a more general role on ion transport or membrane function.