Prostaglandins are vasoactive agents which have potent and varied effects depending on the species, conditions and organs tested. The clinician wishing to gain a significant overview of the field from current research literature has a demanding task for himself. A review of biologic interactions is exactly what is needed in a consideration of possible clinical applications of prostaglandins. Thus, it is necessary first to recount the last five years' advances in prostaglandin research. Only then will the listing and discussion of some diseases soon to benefit from the application of research be meaningful.

Vascular and nonvascular smooth muscles in 12 different organs from the gastrointestinal, respiratory, and urogenital tracts of the rabbit, cow, dog, sheep, pig, and rat were examined for prostaglandin I2 (PGI2) synthase immunoreactivity by indirect immunocytofluorescence using monoclonal antibodies against the enzyme. Each of 35 different smooth muscle layers tested stained for the PGI2 synthase antigen except the circular smooth muscle of the rabbit large intestine. Interestingly, PGI2 synthase-positive fluorescent staining of smooth muscle was always observed to be associated with both the nuclear and plasma membranes. Our results indicate that most smooth muscle, both vascular and nonvascular, has the capacity to synthesize PGI2. Moreover, the fact that the PGI2 synthase antigen is associated with at least two different organelles in each cell suggests that there are two independent PGI2-synthesizing systems in smooth muscle; one on the nuclear membrane, and one on the plasma membrane. PGI2 formed at these different sites may subserve different functions within the same cell.

Prostaglandin forming cyclooxygenase was quantified using an oxygen-uptake assay in five tissues during the last trimester in pregnant rabbits. At Day 20 of pregnancy cyclooxygenase activity was sevenfold greater in the placenta (147 to 204 U/g) than in the amnion, splanchnopleure, decidua, or uterus. Cyclooxygenase activity increased during gestation (P<0.03); the major change in activity occurred in the amnion (from 6 U/g at 20 days to 228 U/g on Day 30; P<0.01). These observations support the idea that prostaglandin synthesis increases near the time of parturition.

Lipoxygenase catalyzes its own destruction during oxygenation of fatty acid substrates. The destruction is first order with respect to enzyme. The rate constant for this inactivation (κ2) has a characteristic value for each fatty acid substrate. The values are greater for acids having correspondingly higher degrees of unsaturation. In the presence of product, the enzyme loses activity 10 times faster with both substrates, fatty acid and oxygen, present than with either alone. We have confirmed that oxygenation of fatty acids by lipoxygenase occurs with a kinetic lag period which can be abolished by adding product hydroperoxides. Product hydroperoxides play an essential role in the over-all autocatalytic reaction. We have further shown that the lag period may be extended as a result of inhibition of the enzyme by polyenoic acid substrates. The previously reported inhibition of lipoxygenase by GSH peroxidase in the presence of glutathione appears to be due to the removal of the hydroperoxide product. These findings as well as those of others may be accommodated by a kinetic model in which distinct roles exist for both the product and the fatty acid substrate in a manner allowing product binding only at the product site whereas fatty acid substrates may bind at either site.

An enzymic system of sheep vesicular gland which forms prostaglandins showed a time-dependent, concentration-dependent activation by phenol before full dioxygenase activity could be manifested. The activation process could be reversibly inhibited by o-phenanthroline. Aspirin and indomethacin did not instantly inhibit the dioxygenase, but acted in a time-dependent, concentration-dependent manner to block full activity of the synthetic system in an irreversible manner. The enzyme preparation was protected from the inhibitory action of these drugs by the presence of o-phenanthroline.