ヒト血小板凝集及び凝集阻害に対するプロスタグランジンの作用機序

Based on the previous report concerning the structure-activity relationship in which inhibiting and stimulating agents for platelet aggregation were able to bind both receptors of human platelet for aggregation and its inhibition, the present experiment was performed to study on the effect of prostaglandins (PGE1, PGI2 and PGD2) on the aggregation and its inhibition of human platelets.
Assuming that PGE1 and PGD2 have conformations for inhibition of platelet aggregation and those for aggregation, changes of cyclic AMP (cAMP) content and of ultrastructure of platelets in the presence of 2', 5'-dideoxyadenosine (DDA, an inhibitor of adenyl cyclase), PGE1 and PGD2 were investigated. When treated with physiological saline, PGE1, PGD2 or DDA alone, aggregation of the platelets was not observed. The platelets were solitarily dispersed. Though most of the platelets showed smooth surface, some platelets showed slight, small elevation and conical depression on the surface. A few platelets possessed one or two short projection at the margin, but no long projection was observed.
The platelets treated with PGE1 or PGD2 in combination with DDA showed markedly elongated projections which is one of the ultrastructural characteristics of activated form of platelets, and were finally aggregated. The most platelets gathered in groups were discoid in form and others showed irregular forms. They had one or sometimes several long pseudopods. It was noted that the pseudopods protruded from the marginal region of the platelets, and were contact with pseudopods of other platelets. The long pseudopods supposed to be the elongation of the spiny and short projections described above. At first, small protrusions appeared on the entire surface of the platelets. They showed a clear tendency to adhere to each other, formed small and larger aggregates, and resulted in more and more firm aggregation. This feature may represent the first stage of transformation for aggregation of platelets. The round protrusion became large in size and increase in number.
The present study pointed out the importance of the concomitant presence of receptors for the aggregation and its inhibition in the platelet plasma membrane.