The effect of low-density lipoproteins on the synthesis of cyclic nucleotides induced by prostacyclin in isolated platelets.

Abstract

Isolated platelets are strongly sensitized by the presence of low-density lipoproteins (LDL) so that they aggregate with very low concentrations of other agonists or exhibit spontaneous aggregation. Prostacyclin (PGI2) is a potent inhibitor of aggregation, but its action was reversed by LDL. This effect of LDL was accompanied by a decrease in the synthesis of cyclic AMP induced by PGI2, but its efficacy depended on the relative concentrations of LDL and PGI2. PGI2 also enhanced the synthesis of cyclic GMP, but this was completely reversed by the presence of LDL. LDL did not remove inhibitory prostaglandins, e.g. E1, from their receptor sites. The lipoproteins also decreased cyclic AMP synthesis induced by forskolin, which has its effect on the GTP-sensitive protein or the catalytic unit of the adenylate cyclase enzyme complex. It is proposed that LDL may act on the enzyme catalytic unit via an inhibitory GTP-sensitive protein or by a separate mechanism which indirectly impedes the production of cyclic AMP.