Effects of forskolin and cilostazol on clot retraction.
We examined the effects of two inhibitors of aggregation of human platelets the, Forskolin and Cilostazol on clot retraction. Both substances suppressed clot retraction in a dose-dependent way. Both suppress platelet aggregation because of an increase in intercellular cyclic AMP, but there was no close correlations were shown between suppression rate for clot retraction and cyclic-AMP content in platelets in the clot in each substance. Furthermore, although it has been considered that actomyosin in platelets is a major contractile source for clot retraction and that failure of actin polymerization results suppression of clot retraction. As it was difficult to obtain active actin from platelets of the reagents on the polymerization. Cilostazol accelerated actin polymerization, whereas Forskolin did not. From these findings, it was considered that the effects of both substances on clot retraction could not be interpreted directly just by the increasing effect for intracellular cyclic-AMP. Clot retraction is consider to be a in vitro model of hemostasis and its contractile force is supplied from platelets (1,2,3). Experiments used prostaglandin E-1 revealed that elevation of cyclic-AMP (c-AMP) would regulate the clot retraction, and experiments used cytochalasin B demonstrated that actomyosin is responsible to the retraction (4,5). Many date demonstrate that elevation of c-AMP level suppresses platelet aggregation (6,7). c-AMP, therefore, should play a key role on platelet activation. Forskolin and Cilostazol are newly-developed reagents as a suppress for platelet functions. Pharmacological action of these substances have been interpreted to process increase effect for intracellular c-AMP of platelets(8,9). If so, both substances should show some effect on clot retraction. Under this assumption, we examined the effects.
Sannomiya
Y
Y
Department of Laboratory Medicine, Osaka City University Medical School, Japan.
Tatsumi
N
N
Okuda
K
K
D000199:Actins / Q000378:metabolism; D000328:Adult; D001393:Azoles / Q000494:pharmacology*; D000077407:Cilostazol; D003018:Clot Retraction; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D014783:Viscosity
D000199:Actins; D001393:Azoles; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D005576:Colforsin; D000242:Cyclic AMP; D000077407:Cilostazol