Delta13-reductase dependent metabolism of prostaglandins in the mammalian brain and eye.
This paper describes the distribution of NAD+-dependent 15-hydroxy prostaglandin dehydrogenase (delta13-reductase) in the mammalian brain and eye tissues. In addition, an NADH-dependent 15-ketoprostaglandin delta13-reductase (15-PGDH) activity was determined in the brain and eye tissue of some species. The rabbit brain and eye tissues were obtained after arterial perfusion with PBS buffer while the monkey, bovine and porcine tissues were obtained without any treatment. [3H]-PGF2alpha or [3H]-15-keto-17-phenyl-18,19,20-trinor-PGF2alpha1-1-isopropy l ester was incubated with different eye tissue preparations under various conditions. No 15-PGDH activity was observed in the monkey brain while 14% of exogenous PGF2alpha was metabolized to its 15-keto-13,14-dihydro-metabolite by the porcine brain. The 15-PGDH activity in the monkey eye tissue was undetectable. Both brain and different eye tissues hydrolysed 15-keto-17-phenyl-18,19,20-trinor-PGF2alpha-1-isopropyl ester to its free acid and the free acid was further metabolized to 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha by the reduction of 13,14-double bond indicating the presence of a delta13-reductase in these tissues. These data suggest that besides the presence of esterases the mammalian brain and eye tissues possess variable amounts of delta13-reductase in spite of their low 15-PGDH activity which may be of importance in physiology and drug metabolism of these tissues.
Basu
S
S
Glaucoma Research Laboratories, Pharmacia & Upjohn, Uppsala, Sweden.
Stjernschantz
J
J
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002924:Ciliary Body / Q000201:enzymology; D003315:Cornea / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005123:Eye / Q000201:enzymology*; D000882:Haplorhini; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007498:Iris / Q000201:enzymology; D009243:NAD / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D013552:Swine; D014316:Tritium
D011453:Prostaglandins; D009243:NAD; D014316:Tritium; C088172:15-keto-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-1-isopropyl ester; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase