Prostaglandins, thromboxane, leukotrienes and the cerebral circulation in health and disease.

Abstract

Arachidonic acid is ubiquitously distributed throughout the body and its derivatives form an extraordinary and bewildering array of compounds of widely differing properties. It is most unwise to generalize about how a given cell or tissue will utilize each pathway. This system responds to both physiological and pathological stimuli but the respective roles of the various products can be very difficult to unravel as will become all too apparent. The recent British Medical Bulletin (1983) provides an excellent overview of the subject. Von Euler (1936) created the term “prostaglandin” to christen the depressor, smooth muscle–stimulating acidic lipid that he and Goldblatt had demonstrated in human seminal plasma. Bergstrom began to determine the structure of this group of compounds in 1947 with publication in the early 1960s (for review, see Bergstrom et al. 1968). Following the isolation and description of the effects of the primary and relatively stable prostaglandins (PGF2 α, PGE1,PGE2, PGD2, etc.) came the discovery that prostaglandin synthesis was inhibited by the non–steroidal antiinflammatory agents such as indomethacin and aspirin (Vane 1971). Certain discrepancies became apparent in the period 1970–1976 between the effects of prostaglandin synthesis inhibition and the effects of the known endogenous prostaglandins. Then, in rapid succession, came the description of the short-lived derivatives of arachidonic acid metabolism, including rabbit aortacontracting substance (Palmer et al. 1973), the cyclic endoperoxides, PGG2 and PGH2, and thromboxane A2 and its inactive metabolite thromboxane B2 (Samuelsson et al. 1978, for review).