Effects of cryptolepine on collagen-induced aggregation and on the mobilization and metabolism of arachidonic acid by rabbit platelets |
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| Institution: | 1. Department of Pharmacology, New York Medical College, Valhalla, NY 10595, U.S.A.;2. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, U.S.A.;1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark;2. Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy;3. Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016, Shenyang, China;1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA;2. Translational Oncology Program, University of Illinois Cancer Center, Chicago, IL 60612, USA;1. Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China;2. School of Pharmacy, Henan University, Kaifeng 475004, China;3. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark;1. Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany;2. Department of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel;3. Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, University of Cologne, 50931 Cologne, Germany;4. German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany;5. Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany;1. Laboratory of Nanotechnology for Precision Medicine, Istituto Italiano di Tecnologia, Genoa 16163, GE, Italy;2. Department of Biomedical and Biotechnological Sciences, Università di Catania, Catania 95123, CT, Italy;3. Department of Pharmacy, Università degli Studi di Napoli Federico II, Naples 80131, NA, Italy;4. Facolta di Medicina e Chirurgia, Università degli Studi di Enna “Kore”, Enna 94100, EN, Italy |
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| Abstract: | 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 μM) 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 μg/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 μM) dose-dependently inhibited thrombin (1.5 U/ml) and A23187 (2.5 μM)-induced release of 14CAA] from platelet membrane phospholipid pools. The percentage inhibition of A23187-induced 14CAA] release was 31.3 ± 4.3% (50 μM) and 79.3 ± 5.4% (100 μM), while thrombin-induced release was inhibited by 39.2 ± 2.4% (50 μM) and 68.2 ± 3.6% (100 μM).4. At near maximal concentration (100 μM) which significantly inhibited secondary aggregatory response and 14CAA] release, cryptolepine had no effect on the platelet metabolism of 14CAA] 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 not effect on platelet cyclooxygenase and lipoxygenase activities of platelets. |
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