Dual effects of bradykinin on prostaglandin metabolism: relationship to the dissimilar vascular actions of kinins.
Generation of a prostaglandin of the F series by bovine mesenteric veins in response to bradykinin may depend on increased synthesis of PGE and conversion of the latter to PGF after activation of PGE 9-ketoreductase by the kinin. The prostaglandin then mediates the constrictor action of bradykinin on the bovine mesenteric vein. A high speed supernatant (HSS) fraction of bovine mesenteric blood vessels contains the highest activity of PGE 9-ketoreductase. Incubation of PGE2 with HSS at 37 degrees C in the presence of a NADPH generating system resulted in time-dependent conversion of PGE2 to PGF2alpha. Bradykin (0.01mM) more than doubled conversion of PGE2 to PGF2alpha by the PGE 9-ketoreductase obtained from mesenteric veins whereas the kinin had little effect on enzymic activity of the HSS fraction of mesenteric arteries. However, after inhibition of kininase catabolism, bradykinin increased PGE 9-ketoreductase activity of arteries and veins to the same degree. Prostaglandin release from veins by bradykinin appears essential to contraction of mesenteric venous strips evoked by the polypeptide as indomethacin treatment abolished this effect. PGE 9-ketoreductase may be an important prostaglandin regulatory mechanism of the vascular wall whereby the functional consequences of changes in rates of prostaglandin synthesis are governed by determining the ratio of PGE to PGF within vascular tissue. Constriction of bovine mesenteric veins evoked by bradykinin may, therefore, depend on increased prostaglandin synthesis and conversion of newly formed PGE to PGF, both steps being affected by the kinin.
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D007705:Kinins / Q000494:pharmacology*; D008642:Mesenteric Veins / Q000201:enzymology / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism*; D011460:Prostaglandins F / Q000096:biosynthesis / Q000378:metabolism*
D007705:Kinins; D011458:Prostaglandins E; D011460:Prostaglandins F; D000429:Alcohol Oxidoreductases; D001920:Bradykinin