Differential production of prostaglandins D2 and E2 and of an unusual prostanoid by chick spinal cord and meninges in vitro.
In order to specify the source of locally synthesized prostaglandin (PG) E2 which is able to saturate the large class of low affinity PGE2 receptors in chick spinal cord, bioconversion of [1-14C]arachidonic acid into prostanoids was studied in homogenates of chick spinal cord and meninges first without addition of exogenous glutathione (GSH). Homogenates of spinal cord produced 14C-labeled PGE2, PGD2 and PGF2 alpha. Homogenates of meninges accumulated much larger amounts of [14C]PGE2 than spinal cord and surprisingly a 14C-labeled arachidonate metabolite referred to as compound Y. Compound Y generation, which was inhibited by indomethacin and enhanced by esculetin, was therefore mediated through the cyclooxygenase pathway. The fact that no labeled compound Y was detected in homogenates incubated with [3H]PGD2 or [3H]PGE2 indicated that compound Y was not a degradation product of PGs. Secondly, after addition of exogenous GSH, 14C-labeled compound Y was totally converted into [14C]PGE2. The compound Y which is converted into PGFs after a strong reduction with NaBH4 and into PGE2 after a mild reduction with GSH-hemin system or SnCl2 was therefore assumed to be a 15 hydroperoxy-PGE2 (15 HP-PGE2). These results suggest that PGE2 can be synthesized in meninges either by the classical isomerization of PGH2 or by isomerization of PGG2 followed by a GSH-sensitive reaction.
Vesin
M F
MF
Institut d'Histologie et d'Embryologie, Faculté de Médecine, Université de Lausanne, Switzerland.
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001894:Borohydrides / Q000494:pharmacology; D002645:Chickens; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008578:Meninges / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D013116:Spinal Cord / Q000378:metabolism*
D001894:Borohydrides; D016718:Arachidonic Acid; C048495:15-hydroperoxyprostaglandin E2; C025364:sodium borohydride; D015237:Dinoprost; D005978:Glutathione; D015232:Dinoprostone; D015230:Prostaglandin D2