Metabolism of prostaglandin E₁ in dog kidneys

Abstract

Summary1. The biotransformation of prostaglandin E1 (PGE,) was studied in the isolated, perfused dog kidneys.2. An average 43% of PGE, was converted into the less polar metabolite I by a single passage through the kidney. As the re-circulation of the perfusate continued, PGE1 was converted not only into metabolite I but also the least polar metabolite II. The velocity of the conversion of PGE1 into metabolite I was significantly greater than that into metabolite II. Usually, six passages elapsed before maximum degradation of PGE1 occurred. 3. Further separation with silicic acid column chromatography and gas-liquid chromatography showed that metabolite II consists of two individual metabolites, metabolite Ila and metabolite Ilb. 4. The present study indicates that the kidney biotransforms PGE1 rather rapidly into three metabolites which are less polar than PGE1.

Relationship between the chemical structure of prostaglandins and their vasoactivities in dogs

“…However, the magnitude of the depressor action of intravenous injection of PGA1 or PGA2 is generally greater than that of PGE1 or PGE2. Many investigators (Ferreira & Vane, 1967;Horton & Jones, 1969 ;McGiff et al, 1969;Nakano & Cole, 1969;Pike et al, 1968) have attributed this difference in the depressor response to the greater metabolic degradation of intravenously injected PGE1 or PGE2 by 15-hydroxy-prostaglandin dehydrogenase in the lungs (AnggArd & Samuelsson, 1964, 1966Nakano, 1970a). The A10 double bond appears to exert more potent vasodilator action since the vasodilator action of PGA compounds is much greater than that of AY-22093.…”

“…1 la-, 15S-dihydroxy-9-keto-prostanoic acid (dihydro-PGE,) and 1la-, 15S-dihydroxy-9, 15-diketo-prostanoic acid (15-ketodihydro-PGE1) were also synthesized by catalytic hydrogenation (using rhodium as a catalyst) in this laboratory from PGE1 and 15-keto-PGE1, respectively, by the method described by Bergstrom, Ryhage, Samuelsson & Sjovall, 1963). All three metabolites were purified by silicic acid chromatography and thin-layer chromatography using slight modifications (Nakano, 1970a(Nakano, , 1970b(Nakano, , 1971) of the method described by Samuelsson (1963) and Green & Samuelsson (1964).…”

“…Several investigators (Bergstrom & von Euler, 1963 ;Horton & Main, 1963, 1966Pike, Kupiecki & Weeks, 1967;DuCharme, Weeks & Montgomery, 1968;Nakano & McCurdy, 1968;Nakano & Cole, 1969) showed that, when administered intravenously, both PGEand PGA-compounds are potent depressor agents whereas PGF compounds are moderate pressor agents in rats and dogs. PGE-compounds are effectively inactivated by a single passage through the lungs (Ferreira & Vane, 1967;Nakano, 1970a) whereas PGAcompounds are more resistant to metabolism in the lungs (Horton & Jones, 1969;McGiff, Terragno, Strand, Lee, Lonigro & Ng, 1969). Hence, it is rather difficult to assess the relationship between the structure of prostaglandins and their direct vasoactivities when one compares the depressor or pressor effect of different prostaglandins administered intravenously.…”

“…PGE-compounds are effectively inactivated by a single passage through the lungs (Ferreira & Vane, 1967;Nakano, 1970a) whereas PGA-compounds are more resistant to metabolism in the lungs (Horton & Jones, 1969; McGiff, Terragno, Strand, Lee, Lonigro & Ng, 1969). Hence, it is rather difficult to assess the relationship between the structure of prostaglandins and their direct vasoactivities when one compares the depressor or pressor effect of different prostaglandins administered intravenously.…”

Metabolism of Prostaglandin E1 in Stomach, Jejunum Chyle and Plasma of the Dog and the Rat

“…3 paper and washed with distilled water. After evaporation under reduced pressure, the extract was separated with discontinuous silicic acid column chromatography using different ratios of the solvent mixture of ethyl acetate: toluene as described previously [14][15][16]. PGEI was eluted with 70% ethyl acetate in toluene, whereas less polar metabolites, l la-hydroxy-9, 15-diketo-13-prostaenoic acid (15--keto-PGEI) and 1lce-hydroxy-9, 15-diketo-prostanoic acid (15-keto-dihydro-PGEI) were eluted with 40% ethyl acetate in toluene.…”