Prostaglandin endoperoxides and thromboxanes: role in platelets and in vascular and respiratory smooth muscle.

1. Two groups of unstable (t 1/2 = 5 min) endoperoxides, PGG and PGH compounds, have been isolated and shown to be precursors of the prostaglandins. 2. A new group of compounds (thromboxanes) derived from the endoperoxides has been discovered. Thromboxanes have so far been found in platelets, leucocytes, lung tissue, spleen, kidney and umbilical artery. In platelets the thromboxane constitute the major products derived from the endoperoxides. 3. A highly unstable (t 1/2 = 30-40 s) intermediate, thromboxane A2, between the endoperoxides and thromboxane B2 has been detected. Structural work indicates that it has a bicyclic oxaneoxetane structure. 4. Thromboxane A2 induces platelet aggregation and causes contraction of the isolated rabbit aorta. Rabbit aorta contracting substance (RCS) discovered by PIPER and VANE consists mainly of thromboxane A2 and to some extent of the endoperoxides PGG2 and PGH2. 5. Endoperoxides and thromboxanes are essential for platelet aggregation. Platelet cyclo-oxygenase deficiency gives rise to a hemostatic defect due to an abnormal release mechanism. 6. The endoperoxides have unique actions on vascular and air-way smooth muscle. The effects are not due to conversion to the stable prostaglandins (PGE, PGF etc). 7. The biologically active compounds formed from polyunsaturated fatty acids via the cyclo-oxygenase catalyzed pathway can be divided into three groups depending on the stability, viz. the stable prostaglandins (PGE etc.), the endoperoxides (PGG and PGH) and the thromboxanes.