Stimulation of vascular prostacyclin (PGI2) production by human serum.
Prostacyclin (PGI2) synthesis by chopped rings of rat aorta was measured by radioimmunoassay (RIA) of its stable hydrolysis product 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha). 6-oxo-PGF1 alpha production by matched groups of aortic rings incubated at 37 degrees in human citrated plasma (PPP) or serum were compared. Serum was prepared by the addition of calcium chloride to citrated plasma and agitation for 3 hr at 37 degrees; the serum was expressed from the coagulum so formed. At the start of an incubation, immediately after the addition of the aortic rings, no 6-oxo-PGF1 alpha was detectable either in plasma or in serum. As described previously, in plasma 6-oxo-PGF1 alpha rose asymptotically toward a plateau at about 30 min. In serum the rapid initial production was prolonged and the increase in 6-oxo-PGF1 alpha concentration was almost linear for 60 min (r = 0.78, P less than 0.001). Production of 6-oxo-PGF1 alpha in serum at 4, 8, 30 and 60 min exceeded that in plasma by factors of 1.48, 1.67, 3.60 and 5.71 respectively (P less than 0.005 at each time). Similar stimulatory activity was found in serum derived from platelet-rich plasma (PRP-S) and that derived from platelet-poor plasma (PPP-S). It was heat stable (100 degrees for 5 min) but was lost following dialysis against an isotonic balanced salt solution. It was not restored by adding calcium chloride to such dialysed serum, and no stimulatory activity was generated if PPP was agitated at 37 degrees for 3 hr without the addition of calcium chloride. The stimulatory activity was not inhibited by cycloheximide. It is concluded that a small heat-stable molecule is generated during coagulation of plasma that stimulates PGI2 synthesis by rat aorta in vitro. Its mechanism of action does not depend on de novo protein synthesis.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001790:Blood Physiological Phenomena; D001792:Blood Platelets / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003956:Dialysis; D011464:Epoprostenol / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010949:Plasma / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats
D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D011464:Epoprostenol