Effects on the buoyant density of rabbit platelets of ADP and agents that
increase the concentration of cyclic AMP
MA Packham, DW Perry, RL Kinlough-Rathbone, ML Rand, MA Guccione, RM Evans and JF Mustard
Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to
deaggregate and then separated into density subpopulations by
centrifugation through discontinuous Stractan density gradients. Although
ADP causes little or no release of the contents of the amine storage
granules of rabbit platelets, ADP caused a decrease in platelet density as
compared with control platelets subjected to the same procedures except for
exposure to ADP. The density change persisted for at least four hours. The
apparent size of platelets stimulated with ADP increased initially, but
returned to control values during a one-hour period. A similar decrease in
platelet density was observed with an albumin density gradient. Under
conditions in which aggregation did not occur in response to ADP with
ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease
in platelet density was observed. Agglutination with polylysine did not
change platelet density. Thus, not only agents such as thrombin and plasmin
that cause the release of the contents of the platelet granules decrease
platelet density, but ADP also has this effect. Platelets would be exposed
to all of these stimuli during thromboembolic processes, and their effect
on platelets may account for the decrease in platelet density observed
previously in experiments with rabbits with indwelling aortic catheters.
Agents that increase the concentration of cyclic AMP (cAMP) in platelets
(PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased
platelet density. This effect persisted when the platelets were washed and
resuspended in fresh medium and was also demonstrable in plasma. Platelet
size was gradually increased by prostaglandin E1 (PGE1) which maintains
platelets in a disc shape and does not cause the release of granule
contents, indicating that the decrease in platelet density caused by PGE1
may be attributable to platelet swelling.
Volume 65,
Issue 3,
pp. 564-570,
03/01/1985
Copyright © 1985 by The American Society of Hematology