Prostaglandin levels in isolated brain microvessels and in normal and norepinephrine-stimulated cat brain homogenates.
The levels of PGD2, PGE2, PGF2 alpha and 6-keto-PGF1 alpha (6KF1 alpha) produced from endogenous arachidonic acid (AA) were quantitated in cat cerebral cortical homogenates and microvessels isolated from cat cerebral cortex using gas chromatography/mass spectrometry (GC/MS). There was a six-fold enrichment of 6KF1 alpha levels in isolated microvessels, compared to homogenates, suggesting that 6KF1 alpha is of vascular, rather than neuronal origin. In order to further understand any possible role that norepinephrine (NE) might have on modulation of PG synthesis, we studied the effects of 0.5 mM NE on PG synthesis from endogenous AA and from 3H-PGG2, the endoperoxide precursor of PGs. In cat cortical homogenates NE induced a 74% increase in PGD2 and PGF2 alpha, a 62% increase in PGE2, and a 36% increase in 6KF1 alpha, as measured by GC/MS. NE caused a twofold increase in the conversion of 3H-PGG2 to 3H-PGF2 alpha, with a concomitant decrease in 3H-PGE2 and 3H-6KF1 alpha formation, and no change in 3H-PGD2 synthesis. NE had no effect on the total conversion of 3H-PGG2 to 3H-PGs, nor on the breakdown of 3H-PGG2 in the absence of brain tissue. We conclude that NE stimulates extravascular synthesis of PGD2, PGE2 and PGF2 alpha by stimulation of the prostaglandin synthetase complex, in addition to NE's stimulatory effect on the conversion of PGG2 to PGF2 alpha, and that the lack of effect on NE on 6KF1 alpha synthesis reflects either a failure to achieve an adequate concentration at the vascular tissue, or an absence of the mechanism whereby NE stimulates PG synthetase.
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011449:Prostaglandin Endoperoxides / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011457:Prostaglandins D / Q000378:metabolism
D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D011457:Prostaglandins D; D009638:Norepinephrine