Kallikrein stimulates prostacyclin production in bovine vascular endothelial cells.
Cultured endothelial cells isolated from bovine carotid aorta produce prostacyclin (prostaglandin I2) and a small amount of prostaglandin E2. The effects of kallikrein (EC 3.4.21.8) on the release of prostacyclin from the cells were studied with the radioimmunoassay technique. Kallikrein stimulated the release of prostacyclin in a dose-dependent manner. The maximal stimulation reached up to 9.2-fold at 0.1 micrograms/ml of kallikrein. The effect was not associated with the activation of the fatty acid cyclooxygenase, but with the stimulation of arachidonic acid release. But kallikrein itself did not have phospholipase activity. On the other hand, at the same doses, kallikrein failed to induce platelet aggregation or enhance platelet aggregation induced by collagen. Our findings suggest that the vasodilator effect of kallikrein is mediated in part by prostacyclin production. Furthermore, we investigated the possibility that the stimulatory effect of kallikrein on prostacyclin production in endothelial cells is associated with kinin formation. Bradykinin and lysylbradykinin (kallidin) also stimulated the release of prostacyclin, but the effects were far less than that of kallikrein. And the stimulation due to the addition of both kallikrein and bradykinin on prostacyclin and arachidonic acid release was not competitive or additive, but synergistic. Moreover, even if fetal calf serum was incubated with kallikrein, bradykinin was not detected at all. When kallikrein was pre-incubated with aporotinin, which is an inactivator of kallikrein, the effect of kallikrein was completely abolished. These findings suggest that the stimulatory effect of kallikrein on the release of prostacyclin from vascular cells is possibly not due to kinin formation, but to other substance(s) produced by this serine proteinase.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002339:Carotid Arteries / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D007609:Kallidin / Q000494:pharmacology; D007610:Kallikreins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
D007609:Kallidin; D003094:Collagen; D011464:Epoprostenol; D010741:Phospholipases A; D010738:Type C Phospholipases; D007610:Kallikreins; D001920:Bradykinin