The Effect of Lanosterol on Platelet Aggregation in Human Platelets

Summary

It has been reported that lanosterol can sensitize isolated rat platelets to agonists such as ADP and thrombin (4). The purpose of this paper was to determine whether lanosterol had similar effects on human platelets and whether this was achieved by changes in membrane fluidity. Lanosterol did increase the sensitivity of human platelets, particularly to adrenaline and ADP at concentrations as low as 5 mg.L^-1 when added from solutions in ethanol. At similar concentrations cholesterol, 4-cholesten-3-one or ethynyloestradiol had either no effect or were inhibitory. Measurement of membrane fluidity with diphenylhexatriene indicated that lanosterol did not affect membrane fluidity. Incubation of platelets with [⁴C]-mevalonic acid gave rise to a very small incorporation into lanosterol, squalene and farnesol. Sudden activation of the platelets did not accelerate lanosterol synthesis during or after platelet aggregation. It was concluded that lanosterol could only influence platelet behaviour if it came from the plasma. However the concentration of the steroid in both platelets and plasma is ten fold less than that required to sensitise the platelets.

Keywords

Platelet aggregation - Lanosterol - Membrane microviscosity - Mevalonic acid

• References

• 1 McGregor L, Mozaroin R, Renaud S. Effect of different concentrations of an oral contraceptive and of pregnancy on platelet functions and platelet-phospholipid fatty acid composition in rats. In Haemostasis and Thrombosis. pp 565-570 London Academic Press; 1979
• 2 Ciavatti M, Michel G, Renaud S. Biosynthesis of cholesterol and cholesterol precursors in platelets of female rats treated with oral contraceptives. Biochim Biophys Acta 1980; 620: 279-307
• 3 D’Hollander F, Chevallier F. Estimations qualitatives et quantitatives des sterols libres et esterifies du rat in toto et de 23 de ses tissus ou organes. Biochim Biophys Acta 1969; 176: 146-156
• 4 Ciavatti M, Dumond E, Benoit C, Renaud S. Oral contraceptives, lanosterol and platelet hyperactivity in rats. Science 1980; 210: 642-643
• 5 Derksen A, Cohen P. Extensive incorporation of [2-¹⁴C] mevalonic acid into cholesterol precursors in vitro. Biochim Biophys Acta 1973; 248: 7396-7403
• 6 Shattil SJ, Cooper RA. Membrane microviscosity and human platelet function. Biochemistry 1977; 15: 4832-4837
• 7 Hassall DG, Owen JS, Bruckdorfer KR. The aggregation of isolated human platelets in the presence of lipoproteins and prostacyclin. Biochem J 1983; 216: 43-49
• 8 Hassall DG, Forrest LA, Bruckdorfer KR, Marenah CB, Turner P, Cortese C, Miller NE, Lewis B. Influence of plasma lipoproteins on platelet aggregation in a normal male population. Arteriosclerosis 1983; 3: 332-338
• 9 Born GV R. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
• 10 Shinitzky M, Barenholz Y. Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta 1978; 515: 367-394
• 11 Gaintner JR, Jackson DP, Maynert EW. The action of thrombin on platelet 5-hydroxytryptamine. Bull John Hopkins Hosp 1962; 111: 185-197
• 12 Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37: 911-917
• 13 Sulpice JC, Ferezou J. Squalene isolation by HPLC and quantitative comparison by HPLC and GLC. Lipids 1984; 19: 631-635
• 14 Barenholz Y, Yechiel E, Cohen R, Deckelbaum RJ. Importance of cholesterol-phospholipid interaction in determining dynamics of normal and abetalipoproteinaemia red blood cell membrane. Cell Biophys 1981; 3: 115-126
• 15 Miettinen AT. Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res 1982; 23: 466-473
• 16 Liu GL K, Ahrens EH, Schreihman PH, Crouse JR. Measurement of squalene in human tissues and plasma: validation and applications. J Lipid Res 1976; 17: 38-45