SUMMARY

Analogues of archidonic acid used to evaluate structural determinants of prostaglan-din receptor and enzyme specificities. Mol. Pharmacol. 19:242-247 (1981). Using ‘4C-labeled fatty acids (19:4 w6, 19:4 w5, 21:4 w6, and 21:4 w7), radiochemical evidence of the formation of a-nor-, w-nor-, a-homo-, and w-homoprostaglandin endoper-oxides (PGH2), prostacyclins (PGI2), and thromboxanes (TA2) was obtained. Investigation of the biological activities of these compounds indicates that, although 21:4 w6 is a substrate for cyclooxygenase and its endoperoxide, a-homo-PGH2, is a substrate for prostacyclin synthetase and thromboxane synthetase, a-homo-PGH2, a-homo-PGI2, and a-homo-TA2 are inactive on all receptors studied. In contrast, 19:4 w5, precursor to u-nor-PGs, and 19:4 w6, precursor to a-nor-PGs, form endoperoxides which are not only substrates of prostacyclin synthetase and thromboxane synthetase, but also aggregate platelets and contract rabbit aorta spiral strips. Surprisingly, both a-nor-TA2 and co-nor-TA2 are partial agonists at vascular smooth muscle receptors but, unlike their respective endoperoxides, do not aggregate washed human platelets. In contrast, 21:4 co7 is converted to w-homo-PGH2 and co-homo-TA2, which aggregate platelets and are full agonists o