The effects of Ca-antagonists on the thrombin-induced mobilization of radiolabeled arachidonate preincorporated into rat platelets as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products were analyzed in the presence of either Call or Ca2+-substitutes, Sr2+ and Ba2+. Results indicate that following thrombin stimulation (0.2 U/ml) in the presence of Ca2+, nitrendipine (Nit), Cd2+ or Mn2+ reduced the release of arachidonate and the biosynthesis of thromboxane 132- Inhibition of arachidonic acid release and metabolism were also obtained by both Nit and Cd2+ in the presence of Sr2+ and Bat+. Results from studies with a semi-purified phospholipase A2 fraction prepared from rat platelets indicated that the activity was almost unaffected by Nit or Cd2+. From these findings, we concluded that inhibition of platelet-induced release and metabolism of arachidonic acid by the Ca-antagonists tested require intact platelets. These data support the hypothesis of an interaction of these agents at an unknown surface membrane level.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
- TXB2 :
Johnson H: Effects by nifedipine (Adalat) on platelet functionin vitro andin vivo. Thrombos Res 21:523–528, 1981
Ikeda Y, Kikuchi M, Toyama K, Watanabe K, Ando Y: Inhibition of human platelet function by verapamil. Thrombos Haemostas 45:158–161, 1981
Davi G, Novo S, Fiore M, Fodera A, Mattina A, Mazzola A, Strano A: Effects by nitrendipine on thromboxane synthesisin vitro andin vivo. Thrombos Res 28:837–842, 1982
Dahl M-L, Uotila P: Verapamil decreases the formation of thromboxane from exogenous [1-14C] arachidonic acid in human plateletsin vitro. Prost Leukotr Med 17:191–19, 1985
Kiyomoto A, Sasaki Y, Odawara A, Morita T: Inhibition of platelet aggregation by diltiazem. Circ Res 52, suppl I, 115–119, 1983
Blache D, Ciavatti M, Ojeda C: Platelet aggregation and endogenous 5-HT secretion in presence of Ca2−, Sr2+ and Ba2+. Effects of calcium antagonists. Thrombos Res 46:779–791, 1987
Blache D, Ciavatti M, Ojeda C: The effect of calcium channel blockers on blood platelet function, especially calcium uptake. Biochim Biophys Acta 923:401–412, 1987
Rink TJ, Smith SW, Tsien RJ: Cytoplasmic free calcium in human platelets: Ca thresholds and Ca-independent activation for shape-change and secretion. Febs Lett 148:21–26, 1982
Hallam TJ, Rink TJ: Responses to adenosine diphosphate in human platelets loaded with the calcium indicator quin2. J Physiol London 368:131–146, 1984
Ware JA, Johnson PC, Smith M, Salzman EW: Inhibition of human platelet aggregation and cytoplasmic calcium response by calcium antagonists: studies with aequorin and quin2. Circ Res 59:39–42, 1986
Blache D, Ciavatti M: Rat platelet arachidonate metabolism in the presence of Ca2+, Sr2+ and Ba2+: studies using intact platelets and semi-purified phospholipase A2. Biochim Biophys Acta 921:541–551, 1987
Bills TK, Smith JB, Silver MJ: Selective release of arachidonic acid from the phospholipids of human platelets in response to thrombin. J Clin Invest 60:1–6, 1977
Vanderhoek JY, Bryant RW, Bailey JM: 15-hydroxy-5,8,11,13-eicosatetraenoic acid. A potent and selective inhibitor of platelet lipoxygenase. J Biol Chem 255:5996–5998, 1980
Jesse RJ, Franson RC: Modulation of purified phospholipase A2 activity from human platelets by calcium and indomethacin. Biochim Biophys Acta 575:467–470, 1979
Hamberg M, Svensson J, Wakabayashi T, Samuelsson B: Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci USA 71:345–349, 1974
Hamberg M, Svensson J, Samuelsson B: Thromboxanes, a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72:2994–2998
Sneddon JM, Williams KI: Effect of cations on the blood platelet release reaction. J Physiol London 235:625–637, 1973
Best LC, Bone EA, Russel RGG: Strontium ions induce production of thromboxane B2 and secretion of 5-HT in washed human platelets. Biochem Pharmacol 30:635–637, 1981
Pang D, Sperelakis N: Nifidipine, diltiazem, bepridil and verapamil uptakes into cardiac and smooth muscle. Eur J Pharm 87:199–207, 1983
Franson RC, Evans H, Thakkar J, Sperelakis N: Inhibition of human platelet aggregation and calcium dependent phospholipase A2 activity by calcium antagonists: evidence for intracellular effects of calcium slow channel blockers. In: N Sperelakis and J Caulfield (eds) Calcium Antagonists: Mechanism of Action on Cardiac Muscle and Vascular Smooth Muscle. M Nijhoff, Amsterdam, 1984, pp 327–338
Henry PD, Bentley KI: Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 68:1366–1369, 1981
Willis AL, Nagel B, Churchill V, Whyte MA, Smith DL, Mahmud I, Puppione D: Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits. Arteriosclerosis 5:250–255, 1985
Rouleau J, Parmley WW, Stevens J, Wikman-Coffelt J, Sievers R, Mahley RW, Havel RJ: Verapamil enhances receptor-mediated endocytocis of low density lipoproteins by aortic cells in culture. J Am Coll Cardiol 1:1453–1460, 1983
Wade PJ, Lunt DO, Lad N, Tuffin DP, McCullagh KG: Effect of calcium and calcium antagonists on [3H]-PAF-acether binding to washed human platelets. Thrombos Res 41:251–262, 1986
About this article
Cite this article
Blache, D., Ciavatti, M. Effects of organic and inorganic Ca antagonists on rat platelet arachidonic acid metabolism in the presence of Ca2+, Sr2+ and Ba2+ . Mol Cell Biochem 85, 191–196 (1989). https://doi.org/10.1007/BF00577114
- platelet activation
- calcium antagonists
- arachidonic acid metabolism
- metal cations
- phospholipase A2