Metabolism of prostaglandins results in its biological inactivation and since this inactivation is extremely efficient it has generally been assumed that the pulmonary metabolites of prostaglandins have little biological activity. However, recently 15-keto metabolites were found to be more potent than the parent prostaglandins on several isolated smooth muscle preparations. Others have reported that 13, 14-dihydro metabolites showed appreciable biological activities. We have, therefore, examined the effects of both of these metabolites of prostaglandin E2 and F2α on airways and circulation in vivo and also investigated the inactivation of these metabolites by the pulmonary circulation, using a superfusion technique.
The results of the present study clearly demonstrated that, of all those metabolites of prostaglandins studied, 13, 14-dihydro metabolites had marked effects on airways, pulmonary vascular bed and systemic blood pressure of guinea pigs. Moreover, the the potency of these metabolites was roughly the same as that of parent prostaglandins, however other metabolites, 15-keto prostaglandins, were less potent than the parent prostaglandins.
The inactivation of prostaglandins (PGs) is an important characteristics of the pulmonary vascular bed. Although the metabolism of the parent PGs in the pulmonary circulation have been extensively studied, no studies have been made on the inactivation of their metabolites. In the isolated perfused guinea pig lungs, the biological activity of 15-keto PG E2 was least affected by passage through the lungs, while 82% of infused 15-keto F2α was inactivated in one passage. Up to 88% of 13, 14-dihydro-PG E2 suffered inactivation, while only 63% of 13, 14-dihydro PG F2α was inactivated. 13, 14-dihydro-15-keto PG F2α was inactivated only 49%. Thus, within this very closely related group of substances, the degree of inactivation in one passage through the lung differs for each metabolite, and it was also found that a discrepancy existed between E and F groups
Based on these results, it would be conceivable that several of the biological effects of prostaglandins released in anaphylactic shock or in bronchial asthma may be due to a high level of prostaglandin metabolites. The PGs metabolites, such as 15-keto PG E2, 13, 14-dihydro PG F2α and 13'14-dihydro-15-keto PG F2α, the initial activity of which was preserved after the passage through the lung, might function as actual circulating hormones.
