Summary
The requirement for receptor occupancy in thrombin-induced secretion in human platelets
has been studied. When increasing concentrations of thrombin were added to gel-filtered
platelets containing a constant, high concentration of hirudin, dense granule secretion
was initiated at lower thrombin concentrations than those required for α-granule secretion
and aggregation; acid hydrolase secretion required higher concentrations. A 62-fold
excess of hirudin produced abrupt stop of dense granule secretion and a-granule secretion
when added to non-aggregating (no stirring) platelets shortly after thrombin; it had no affect after these secretory process had reached about 30% of
their maximal values. Acid hydrolase secretion was, however, abruptly stopped by hirudin
at any stage. When the platelets were allowed to aggregate, the three secretory processes
increased their rates and were abruptly stopped by hirudin at any stage. Aggregation
(optical) occurred slower than dense granule and α-granule secretion, and was reversed
by hirudin when added before it had reached 30% of its maximum.
It is concluded that a-granule secretion, like dense granule secretion, only requires
a short receptor occupancy to be completed, in contrast to the requirement for sustained
occupancy for acid hydrolase secretion. α-Granule secretion might, however, require
longer occupancy than dense granule secretion. Aggregation is believed to potentiate
secretion through close cell contact and the secretion processes were inhibited by
hirudin through hirudin’s effect on aggregation.
Keywords
Platelets - Thrombin - Hirudin - Aggregation - Dense granule secretion - ɑ-Granule
secretion - Acid hydrolase secretion
