Thromb Haemost 1983; 50(02): 537-540
DOI: 10.1055/s-0038-1665249
Original Article
Schattauer GmbH Stuttgart

Verapamil and Collagen-Induced Platelet Reactions- Evidence for a Role for Intracellular Calcium in Platelet Activation

P Han
The Department of Medicine and Clinical Science, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
,
C Boatwright
The Department of Medicine and Clinical Science, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
,
N G Ardlie
The Department of Medicine and Clinical Science, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
› Author Affiliations
Further Information

Publication History

Received 27 December 1983

Accepted 24 May 1983

Publication Date:
18 July 2018 (online)

Summary

Calcium is considered to have an essential role in various platelet reactions. Using platelets preincubated with Chlortetracycline, a fluorescent divalent cation indicator, and suspended in a calcium free medium, it was shown that collagen-induced intracellular calcium redistribution occurred before the platelet shape change, the release reaction and thromboxane B2 formation. Verapamil, at concentrations which affect intracellular calcium movements, inhibited intracellular calcium redistribution in platelets and the subsequent collagen-induced platelet reactions. Low concentrations of the ionophore A23187 overcame the inhibitory effect of verapamil. These experiments provide evidence that intracellular calcium mobilization is involved in the activation of platelets by collagen. Furthermore, calcium may be released from different cellular pools since platelet secretion, aggregation and thromboxane B2 formation were inhibited at lower concentrations of verapamil than was the platelet shape change.

 
  • References

  • 1 Gerrard JM, Peterson DA, White JG. Calcium mobilization. In Platelets in Biology and Pathology - 2. Gordon JL. (ed) Research Monographs in Cell and Tissue Pathology. Elsevier/North Holland Biomedical Press; Amsterdam: 1981. 5 407-436
  • 2 Ardlie NG. Calcium ions, drug action and platelet function. Pharmacol Ther 1982; 18: 249-270
  • 3 Pickett WC, Jesse RL, Cohen P. Initiation of phospholipase A2 activity in human platelets by the calcium ion ionophore A23187. Biochim Biophys Acta 1977; 486: 209-213
  • 4 Rittenhouse-Simmons S, Deykin D. The activation by Ca2+ of platelet phospholipase A2 . Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate Biochim Biophys Acta 1978; 543: 409-422
  • 5 Shaw JO, Lyons RM. Requirements for different Ca2+ pools in the activation of rabbit platelets. II. Phospholipase activity. Biochim Biophys Acta 1982; 714: 500-504
  • 6 Le Breton GC, Dinerstein RJ, Roth LJ, Feinberg H. Direct evidence for intracellular divalent cation redistribution associated with platelet shape change. Biochem Biophys Res Commun 1976; 71: 362-370
  • 7 Le Breton GC, Sandler WC, Feinberg H. The effects of D2O and chlortetracycline on ADP-induced platelet shape change and aggregation. Thromb Res 1976; 8: 477-485
  • 8 Feinstein MB, Fraser C. Human platelet secretion and aggregation induced by calcium ionophores. Inhibition by PGE1 and dibutyryl cyclic AMP J Gen Physiol 1975; 66: 561-581
  • 9 Charo IF, Feinman RD, Detwiler TC. Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochem Biophys Res Commun 1976; 72: 1462-1467
  • 10 Feinstein MB. Release of intracellular membrane-bound calcium precedes the onset of stimulus-induced exocytosis in platelets. Biochem Biophys Res Commun 1980; 93: 593-600
  • 11 Shaw JO, Lyons RM. Requirements for different Ca2+ pools in the activation of rabbit platelets. I. Release reaction and protein phosphorylation. Biochim Biophys Acta 1982; 714: 492-499
  • 12 Caswell AH, Hutchison JD. Visualization of membrane bound cations by a fluorescent technique. Biochem Biophys Res Commun 1971; 42: 43-49
  • 13 Cameron HA, Ardlie NG. The facilitating effects of adrenaline on platelet aggregation. Prostaglandins Med 1982; 9: 117-128
  • 14 Brown R, Albano JD, Ekins RP, Scherzi AM, Tampion W. A simple and sensitive saturation assay method for measurement of adenosine 3‘-5’ cyclic monophosphate. Biochem J 1971; 121: 561-562
  • 15 Cazenave JP, Packham MA, Mustard JF. Adherence of platelets to a collagen-coated surface: development of a quantitative model. J Lab Clin Med 1973; 82: 978-990
  • 16 Cohn JN. Calcium-entry blockers in coronary artery disease. Circulation 1982; 65 Suppl (Suppl. 01) 1-2
  • 17 Vanhoutte PM. Calcium-entry blockers and vascular smooth muscle. Circulation 1982; 65 Suppl (Suppl. 01) 11-19
  • 18 Thorens S, Haeusler G. Effects of some vasodilators on calcium translocation in intact and fractionated vascular smooth muscle. Eur J Pharmacol 1979; 54: 79-91
  • 19 Church J, Zsoter TT. Calcium antagonistic drugs. Mechanism of action. Can J Physiol Pharmacol 1980; 58: 254-264
  • 20 Owen NE, Feinberg H, LeBreton GC. Epinephrine induces Ca2+ uptake in human blood platelets. Am J Physiol 1980; 239: H483-H488
  • 21 Owen NE, LeBreton GC. Ca2+ mobilization in blood platelets as visualized by chlortetracycline fluorescence. Am J Physiol 1981; 241: H613-H619
  • 22 Le Breton GC, Dinerstein RJ. Effect of the calcium antagonist TMB- 6 on intracellular calcium redistribution associated with platelet shape change. Thromb Res 1977; 10: 521-523
  • 23 Ikeda Y, Kikuchi M, Toyama K, Watanabe K, Ando Y. Inhibition of human platelet functions by verapamil. Thromb Haemostas 1981; 45: 158-161
  • 24 Han P, Boatwright C, Ardlie NG. Inhibition of platelet function by antiarrhythmic drugs verapamil and disopyramide. Thromb Haemostas 1982; 47: 150-153
  • 25 Barnathan ES, Addonizio VP, Shattil SJ. Interaction of verapamil with human platelet a-adrenergic receptors. Am J Physiol 1982; 242: H19-H23