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
