Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig.
Infusion of norephinephrine (NE) (1 - 3 mug/ml/min) into the isolated mesenteric vascular preparation of rabbit resulted in a rise in perfusion pressure, which was associated with the release of prostaglandin E-like substance (PGE) at a concentration of 2.81 +/- 0.65 ng/ml in terms of PGE2. Indomethacin (3 mug/ml) abolished the NE-induced release of PGE. Arachidonic acid (0.2 mug/ml) in the presence of indomethacin did not restore the NE-induced release of PGE. Hydrocortisone (10 - 30 mug/ml) and dexamethasone (2 - 5 mug/ml) also inhibited the NE-induced release of PGE. The inhibitory action of both corticosteroids was abolished by arachidonic acid (0.2 mug/ml). Antigen-induced release of a prostaglandin-like substance (PGs) (43.1 +/- 3.8 ng/ml in terms of PGE2 and a rabbit aorta contracting substance (RCS) from perfused lungs of sensitized guinea pigs was completely abolished by indomethacin (5 mug/ml) or by hydrocortisone (100 mug/ml). Indomethacin, however, increased histamine release up to 280% of the control level, which was 470 +/- 54 ng/ml, while hydrocortisone diminished histamine release down to 30% of the control level. A superimposed infusion of arachidonic acid (1 mug/ml) into the pulmonary artery reversed the hydrocortisone-induced blockade of the release of RCS and PGs. It may be concluded that corticosteroids neither inhibit prostaglandin synthetase nor influence prostaglandin transport through the membranes but they do impair the availability of the substrate for the enzyme.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011458:Prostaglandins E / Q000097:blood / Q000378:metabolism*; D011817:Rabbits
D001095:Arachidonic Acids; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D003907:Dexamethasone; D006854:Hydrocortisone; D009638:Norepinephrine; D007213:Indomethacin