Abstract
Picotamide is a dual TxA2 receptor antagonist/Tx A2 synthetase inhibitor. As the picotamide effect is maximum only after 5–10 min of
incubation, aim of the present work was to study whether the effect of picotamide
could be observed even after wash out of the drug from the external buffer. Platelet
aggregation, serotonin release and changes in intracellular calcium were analyzed
in platelets treated with picotamide and then gel-filtered, in comparison with gel-filtered
platelets treated with picotamide. To exclude the possibility that the inhibitory
effect of picotamide is due to its intracytosolic storage, serotonin release in digitonin-permeabilized
platelets was measured. Platelet aggregation and serotonin release in response either
to U46619, a synthetic agonist of the thromboxane A2 receptor, or arachidonic acid
or collagen, as well as the changes in intracellular calcium concentration after U46619
or arachidonic acid stimulation, were inhibited by picotamide even when it had been
washed out by gel-filtration. Both inhibitions were very similar to that observed
in experiments in which picotamide was present in the medium. As the serotonin release
in digitonin permeabilized platelets presented the same inhibition it may be excluded
that picotamide effect is consequent upon the cytosolic storage of the drug. Since
our results clearly indicate that the action of picotamide persists even after washing
out of the drug from the medium, the idea that this antagonistic effect may be dependent
on its binding to platelet plasma membrane rather than on its cytosolic concentration,
is strongly substantiated. Copyright © 1997 Elsevier Science Ltd
Keywords
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Article info
Publication history
Accepted:
November 22,
1996
Received in revised form:
November 22,
1996
Received:
August 28,
1996
Identification
Copyright
© 1997 Elsevier Science Ltd. Published by Elsevier Inc. All rights reserved.
