ABSTRACT
In the normal physiologic situation, the biological actions of arachidonic acid (AA) metabolites are limited to the local site of biosynthesis as opposed to exerting systemic effects. Therefore, prostaglandins and other AA metabolites are generally considered to be local rather than circulating hormones. A major reason that AA metabolites released at a local site of biosynthesis do not exert systemic effects under normal circumstances is because these compounds are rapidly and efficiently metabolized to biologically inactive metabolites. Thus, the biologically active unmetabolized compounds are prevented from reaching the systemic circulation in sufficient concentration to exert effects at sites distant to the origin of biosynthesis. In addition, some arachidonic metabolites are chemically very unstable, in particular thromboxane A2 (TXA2) and prostacyclin (PGI2), so that spontaneous nonenzy-matic chemical degradation to biologically inactive compounds may be an additional mechanism which limits the biological actions of these compounds to the local site of formation. Such general considerations are reviewed in the first chapter by A. L. Willis.
