Prostacyclin Synthesis Is Stimulated by a Serum Factor Formed During Coagulation

Summary

Fresh aortic rings incubated in serum produce more 6-oxo-PGF_1α, the stable hydrolysis product of prostacyclin, than in plasma or buffer. A method is described of recovering this stimulatory activity from a dialysate of serum, showing that the activity is due to a prostacyclin stimulating factor. This factor is formed during coagulation initiated by the intrinsic pathway but not by the extrinsic pathway or by thrombin. By contrast with a previously described plasma factor, the activity of the prostacy-clinstimulating factor in serum is not greater in serum from patients with renal failure than from healthy controls. The stimulating factor is antagonised by heparin, but differs in other ways from previously described platelet derived stimulating factor(s).

Keywords

Prostacyclin - Aortic rings - Serum factor

• References

• 1 Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A₂and prostacyclin. Pharmacol Rev 1978; 30: 293-331
• 2 Ritter JM, Orchard MA, Blair IA, Lewis PJ. The time course and magnitude of prostacyclin (PGI₂) production by rat aortic rings incubated in human plasma. Biochem Pharmacol 1982; 31: 1163-1165
• 3 Lewis PJ, Orchard MA, Ritter JM. Plasma inhibits and serum stimulates prostacyclin (PGI₂) synthesis by rat aortic rings. Br J Pharmacol 1982; 75: 8
• 4 Ritter JM, Orchard MA, Lewis PJ. Stimulation of vascular prostacyclin (PGI₂) production by human serum. Biochem Pharmacol . 1982 31. in press
• 5 MacIntyre DE, Pearson JD, Gordon JL. Localisation and stimulation of prostacyclin production in vascular cells. Nature 1978; 271: 549-551
• 6 Remuzzi G, Livio M, Cavenaghi AE, Marchesi D, Mecca G, Donati MB, de GaetanoG. Unbalanced prostaglandin synthesis and plasma factors in uraemic bleeding. A hypothesis. Thromb Res 1978; 13: 531-536
• 7 Defreyn G, Vergara DaudenM, Machin SJ, Vermylen J. A plasma factor in uraemia which stimulates prostacyclin release from cultured endothelial cells. Thromb Res 1980; 19: 695-699
• 8 Seid JM, Jones PB B, Hughes P, Tomlinson S, Russell RG G. Stimulation of prostacyclin production from vascular endothelial cells by plasma, serum and platelets under normal and pathological conditions. Vth International Conference on Prostaglandins s. Abstract Book (566) Florence 1982
• 9 Coughlin SR, Moskowitz MA, Zetter BR, Antoniades HN, Levine L. Platelet dependent stimulation of prostacyclin synthesis by platelet derived growth factor. Nature 1980; 288: 600-602
• 10 Ritter JM, Orchard MA, Lewis PJ. Inhibition of vascular epoprostenol [prostacyclin (PGI₂] production in vitro by plasma from healthy subjects and patients with severe renal impairment. Br J Clin Pharmacol 1982; 14: 379-383
• 11 Orchard MA, Blair IA, Ritter JM, Myatt L, Jogee M, Lewis PJ. Radioimmunoassay at alkaline pH: A method for the quantitative determination of prostacyclin. Biochem Soc Trans 1982; 10: 241