calcimycin and cryptolepine

1. We examined the effect of cryptolepine on collagen-induced aggregation and on the mobilization, and metabolism of arachidonic acid in rabbit platelets. 2. Preincubation of platelets with cryptolepine (50-100 microM) did not affect the primary wave of aggregation but resulted in a dose-dependent, surmountable inhibition of the secondary wave of aggregation induced by collagen (5 micrograms/ml). The inhibition by cryptolepine was greater when cryptolepine was incubated with the platelets after the peak of the primary wave of aggregation. 3. Cryptolepine (50-100 microM) dose-dependently inhibited thrombin (1.5 U/ml) and A23187 (2.5 microM)-induced release of 14C[AA] from platelet membrane phospholipid pools. The percentage inhibition of A23187-induced 14C[AA] release was 31.3 +/- 4.3% (50 microM) and 79.3 +/- 5.4% (100 microM), while thrombin-induced release was inhibited by 39.2 +/- 2.4% (50 microM) and 68.2 +/- 3.6% (100 microM). 4. At near maximal concentration (100 microM) which significantly inhibited secondary aggregatory response and 14C[AA] release, cryptolepine had no effect on the platelet metabolism of 14C[AA] to thromboxane B2, HHT and 12 HETE. 5. The present findings suggest that cryptolepine inhibited collagen-induced secondary aggregation through a selective antiphospholipase-like activity. There was no effect on platelet cyclooxygenase and lipoxygenase activities of platelets.

Topics: Alkaloids; Animals; Arachidonic Acid; Blood Platelets; Calcimycin; Cell Membrane; Collagen; In Vitro Techniques; Indole Alkaloids; Indoles; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinolines; Rabbits; Thrombin