Download PDF
Thromb Haemost 1997; 77(03): 555-561
DOI: 10.1055/s-0038-1656005
Platelets
Schattauer GmbH Stuttgart

ADP-mimicking Platelet Aggregation Caused by Rugosin E, an Ellagitannin Isolated from Rosa rugosa Thunb

Che-Ming Teng
1   The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Ya-Fei Kang
1   The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Ya-Ling Chang
1   The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Feng-Nien Ko
1   The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Shu-Chen Yang
2   The School of Pharmacy, Taipei Medical College, Taipei, Taiwan
,
Feng-Lin Hsu
2   The School of Pharmacy, Taipei Medical College, Taipei, Taiwan
› Author Affiliations
Further Information

Publication History

Received 14 May 1996

Accepted after revision 04 November 1996

Publication Date:
11 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 ± 0.1 µM in rabbit platelets and 3.2 ±0.1 µM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by indomethacin, verapamil, TMB-8, BN52021 and GR32191B. Rugosin E-induced thromboxane formation was suppressed by indomethacin, EGTA, PGE,, verapamil, mepacrine, TMB-8 and neomycin. ADP-scavenging agents, such as CP/CPK and apyrase inhibited concentration-dependently ADP (20 εM)-, but not rugosin E (5 εM)-induced platelet aggregation. In thrombin (0.1 U/ml)-treated and degranulated platelets, rugosin E and ADP still caused 63.5 ± 3.0% and 61.2 ± 3.5% of platelet aggregation, respectively. Selective ADP receptor antagonists, ATP and FSBA inhibited rugosin E- and ADP-induced platelet aggregations in a concentration-dependent manner. Both rugosin E and ADP did not induce platelet aggregation in ADP (1 mM)-desensitized platelets. In contrast to ADP, rugosin E did not decrease cAMP formation in washed rabbit platelets. Both rugosin E and ADP did not cause phosphoinositide breakdown in [3H]myo-inositol-labeled rabbit platelets. In fura-2/AM- load platelets, both rugosin E and ADP induced increase in intracellular calcium concentration and these responses were inhibited by ATP and PGEj. All these data suggest that rugosin E may be an ADP receptor agonist in rabbit platelets.

 

  • References

  • 1 Teng CM, Ko FN, Yu SM. Inventory of exogenous factors affecting platelet aggregation isolated from plant sources. Thromb Haemost 1994; 71: 0517-0520
    PubMedSearch in Google Scholar
  • 2 Ross R. The pathogenesis of atherosclerosis – An update. N Engl J Med 1986; 314: 0488-0500
    CrossrefPubMedSearch in Google Scholar
  • 3 Hirsh J. Hyperreactive platelets and complications of coronary artery disease. N Engl J Med 1987; 316: 1543-1544
    CrossrefPubMedSearch in Google Scholar
  • 4 Dinerman JL, Mehta JL. Endothelial, platelet and leukocyte interactions in ischemic heart disease: Insights into potential mechanisms and their clinical relevance. J Am Coll Cardio 1990; 16: 0207-0222
    CrossrefPubMedSearch in Google Scholar
  • 5 Schwartz SM, Heimark RL, Majesky MW. Developmental mechanisms underlying pathology of arteries. Physiol Rev 1990; 70: 1177-1209
    CrossrefPubMedSearch in Google Scholar
  • 6 Gordon JL. Extracellular ATP: effects, sources and fate. Biochem J 1986; 233: 0309-0319
    CrossrefPubMedSearch in Google Scholar
  • 7 McClure MO, Kakkar A, Cusack NJ, Bom GVR. Evidence for the dependence of arterial haemostasis on ADP. Proc R Soc London Ser B 1988; 234: 0255-0262
    CrossrefPubMedSearch in Google Scholar
  • 8 Kim BK, Zamecnik P, Taylor G, Guo MJ, Blackburn GM. Antithrombotic effect of ß,ß’-monochloromethylene diadenosine 5',5”’-Pl, P4-tetraphos- phate. Proc Natl Acad Sci USA 1992; 89: 11056-11058
    CrossrefPubMedSearch in Google Scholar
  • 9 Hatano T, Ogawa N, Shingu T, Okuda T. Rugosins D, E, F and G dimeric and trimeric hydrolyzable tannins with valoneoyl group(s), from flower petals of Rosa rugosa Thunb. Chem Pharm Bull 1990; 38: 3341-3346
    CrossrefPubMedSearch in Google Scholar
  • 10 Oukda T, Hatano T, Yazaki K, Ogawa N. Rugosin A, B, C and Praecoxin A tannins having a valoneoyl group. Chem Pharm Bull 1982; 30: 4230-4233
    CrossrefPubMedSearch in Google Scholar
  • 11 Yoshida T, Maruyama Y, Memon MU, Shingu T, Okuda T. Gemins D, E and F ellagitannins from Geum japonicum. Phytochemistry 1985; 24: 1041-1046
    CrossrefPubMedSearch in Google Scholar
  • 12 Okuda T, Yoshida T, Ashida M, Yazaki K. Tannins of casuarina and stachyurus species. Part 1. Structures of pendunculagin, casuarictin, strictinin casurarinin, casuariin, and stachyurin J Chem Soc Perkin Trans 1983; 1: 1765-1772
    PubMedSearch in Google Scholar
  • 13 Nonaka G, Ishimaru K, Azuma R, Ishimatsu M, Nishioka I. Tannins and related compounds. LXXXV. Structures of novel C-glycosidic ellagitannins, grandinin and pterocarinins A and B. Chem Pharm Bull 1989; 37: 2071-2077
    CrossrefPubMedSearch in Google Scholar
  • 14 Nonaka G, Sakai T, Tanaka T, Mihashi K, Nishioka I. Tannins and related compounds. XCVII. Structure revision of C-glycosidic ellagitannins, cas- talagin, vescalagin, casuarinin and stachyurin, and related hydrolyzable tannins. Chem Pharm Bull 1990; 38: 2151-2156
    CrossrefPubMedSearch in Google Scholar
  • 15 Nonaka G, Harada M, Nishioka I. Eugeniin, a new ellagitannin from cloves. Chem Pharm Bull 1980; 28: 0685-0687
    CrossrefPubMedSearch in Google Scholar
  • 16 Okuda T, Yoshida T, Hatano T, Yazaki K, Ashida M. Ellagitannins of casuarinaceae, stachyuraceae and myrtaceae. Phytochemistry 1982; 21: 2871-2874
    PubMedSearch in Google Scholar
  • 17 Teng CM, Chen WY, Ko WC, Ouyang C. Antiplatelet effect of butylide-nephthalide. Biochim Biophys Acta 1987; 924: 0375-0382
    PubMedSearch in Google Scholar
  • 18 O’Brien JR. Platelet aggregation. Part II. Some results from a new method of study. J Clin Pathol 1962; 15: 0452-0455
    CrossrefPubMedSearch in Google Scholar
  • 19 De Luca M, McElroy WD. Purification and properties of firefly luciferase. Methods Enzymol 1978; 57: 0003-0015
    PubMedSearch in Google Scholar
  • 20 Reimers HJ, Kinlough-Rathbone RL, Cazenave JP, Senyi AF, Hirsh J, Packham MA, Mustard JF. In vitro and in vivo functions of thrombin-treated platelet. Thromb Haemost 1976; 35: 0151-0166
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Huang EM, Detwiler TC. The effect of lithium on platelet phosphoinositide metabolism. Biochem J 1986; 236: 0895-0901
    CrossrefPubMedSearch in Google Scholar
  • 22 Neylon CB, Summers RJ. Stimulation of αj-adrenoceptors in rat kidney mediates increased inositol phospholipid hydrolysis. Br J Pharmacol 1987; 0367-0376
    PubMedSearch in Google Scholar
  • 23 Pollock WK, Rink TJ. Thrombin and ionomycin can raise platelet cytosolic Ca2+to micromolar levels by discharge of internal Ca2+stores: Studies using fura-2. Biochem Biophys Res Commun 1986; 139: 0308-0314
    CrossrefPubMedSearch in Google Scholar
  • 24 Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-3450
    PubMedSearch in Google Scholar
  • 25 Lips PM, Sixma JJ, Schiphorst ME. Binding of adenosine diphosphate to human blood platelets and to isolated blood platelet membranes. Biochim Biophys Acta 1980; 628: 0451-0467
    CrossrefPubMedSearch in Google Scholar
  • 26 Colman RW. Platelet activation: role of an ADP receptor. Seminars in Hematology 1986; 23: 0119-0128
    PubMedSearch in Google Scholar
  • 27 Colman RW. Aggregin: a platelet ADP receptor that mediates activation. FASEB J 1990; 4: 1425-1435
    CrossrefPubMedSearch in Google Scholar
  • 28 Majerus PW, Wilson DB, Connolly TM, Bross TE, Neufeld EJ. Phospho-inositide turnover provides a link in stimulus-response coupling. Trends Biochem Sci 1985; 10: 0168-0170
    CrossrefPubMedSearch in Google Scholar
  • 29 Detwiler TC, Charo IF, Feinman RD. Evidence that calcium regulates platelet function. Thromb Haemost 1978; 40: 0207-0211
    PubMedSearch in Google Scholar
  • 30 Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2and prostacyclin. Pharmacol Rev 1978; 30: 0293-0331
    PubMedSearch in Google Scholar
  • 31 White JG, Gerrard JM. Platelets: a multidisciplinary approach. Raven Press; New York: 1978
    Search in Google Scholar
  • 32 Shen TY, Hwang SB, Chang MN, Doebber TW, Lam MHT, Wu MS, Wang X, Han GQ, Li RZ. Characterization of a platelet-activating factor receptor antagonist isolated from haifenteng (Piper fatokadsura): specific inhibition of in vitro and in vivo platelet-activating factor induced effects. Proc Natl Acad Sci USA 1985; 82: 0672-0676
    CrossrefPubMedSearch in Google Scholar
  • 33 Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science 1984; 225: 1365-1370
    CrossrefPubMedSearch in Google Scholar
  • 34 Feinstein MB, Egan JJ, Sha’nfi RI, White J. The cytoplasmic concentration of free calcium in platelets is controlled by stimulators of cyclic AMP production (PGD2, PGE1foskolin). Biochem Biophys Res Commun 1983; 13: 0598-0604
    PubMedSearch in Google Scholar
  • 35 Waldman SA, Murad F. Cyclic GMP synthesis and function. Pharmacol Rev 1987; 39: 0163-0196
    PubMedSearch in Google Scholar
  • 36 Hoffmann SL, Prescott SM, Majerus PW. The effects of mepacrine and p-bromophenacyl bromide on arachidonic acid release in human platelets. Arch Biochem Biophys 1982; 215: 0237-0244
    CrossrefPubMedSearch in Google Scholar
  • 37 Gabev E, Kasianowicz J, Abbott T, McLaughlin S. Binding of neomycin to phosphatidyl 4,5-bisphosphate (PIP2). Biochim Biophys Acta 1989; 979: 0105-0112
    CrossrefPubMedSearch in Google Scholar
  • 38 Lips PM, Sixma JJ, Schiphorst ME. Binding of adenosine diphosphate to human blood platelets and to isolated blood platelet membranes. Biochim Biophys Acta 1980; 628: 0451-0467
    CrossrefPubMedSearch in Google Scholar
  • 39 MacIntyre DE, Pollock WK, Shaw AM, Bushfield M, MacMillan LJ, McNicol A. Agonist-induced inositol phospholipid metabolism and Ca2+flux in human platelet activation. Adv Exp Biol Med 1985; 192: 0127-0144
    PubMedSearch in Google Scholar
  • 40 Vickers JD, Kinlough-Rathbone RL, Packham MA, Mustard JF. Inositol phospholipid metabolism in human platelets stimulated by ADP. Eur J Biochem 1990; 193: 0521-0528
    CrossrefPubMedSearch in Google Scholar
  • 41 Packham MA, Livne AA, Ruben DH, Rand ML. Activation of phospholipase C and protein kinase C has little involvement in ADP-induced primary aggregation of human platelets: effect of diacylglycerols, the diacylglycerol kinase inhibitor R59022, staurosporine and okadaic acid. Biochem J 1993; 290: 0849-0856
    CrossrefPubMedSearch in Google Scholar
  • 42 Raha S, Jones GD, Gear ARL. Sub-second oscillation of inositol 1,4,5- trisphosphate and inositol 1,3,4,5-tetrakisphosphate during platelet activation by ADP and thrombin: lack of correlation with calcium kinetics. Biochem J 1993; 292: 0849-0856
    PubMedSearch in Google Scholar
  • 43 Hallam TJ, Rink TJ. Responses to adenosine diphosphate in human platelets loaded with the fluorescent calcium indicator quin 2. J Physiol (Lond.) 1985; 368: 0131-0146
    CrossrefPubMedSearch in Google Scholar
  • 44 Mills DCB, Figures WR, Scearce LM, Stewart GJ, Colman RF, Colman RW. Two mechanisms for inhibition of ADP-induced platelet shape change by 5’-fluorosulforyl-benzoyladenosine. J Biol Chem 1985; 260: 8078-8083
    PubMedSearch in Google Scholar
  • 45 Macfarlane DE, Srivastava PC, Mills DCB. 2-Methylthioadenosine [ß-32P]diphosphate. Antagonist and radioligand for the receptor that inhibits the accumulation of cAMP in intact blood platelets. J Clin Invest 1983; 71: 0420-0425
    CrossrefPubMedSearch in Google Scholar
  • 46 Macfarlane DE, Mills DCB, Srivastava PC. Binding of 2-azidoadenosine [ß-32P]diphosphate to the receptor on intact human blood platelets which inhibits adenylate cyclase. Biochemistry 1982; 21: 0544-0549
    CrossrefPubMedSearch in Google Scholar
  • 47 Huang TF, Wang WJ, Teng CM, Ouyang C. Mechanism of action of the antiplatelet peptide, arietin, from Bitis arietans venom. Biochim Biophys Acta 1991; 1074: 0144-0150
    CrossrefPubMedSearch in Google Scholar