The Platelet Dense Tubular System: its Relationship to Prostaglandin Synthesis and Calcium Flux^[*]

Summary

The platelet dense tubular system, an internal smooth endoplasmic reticulum membrane system occupies a pivotal position in the initiation and modulation of platelet activation. The best available evidence suggests platelet prostaglandin and thromboxane synthesis and an internal calcium store critical to platelet activation are both found in the platelet dense tubular system. Studies of the structural, physiologic and chemical properties of thromboxane A₂ support the concept that this product of platelet prostaglandin synthesis acts to carry the calcium from the dense tubular system into the cytoplasm where the calcium is released to initiate contraction of the platelet contractile proteins. Evaluation of platelet phospholipase A₂ suggests that calcium may be critical to activation of this enzyme. Two of the steps occurring during platelet activation which appear to require calcium 1) phospholipase A₂ activation and 2) internal contraction may be linked up in series with the thromboxane A₂ acting as the critical carrier of calcium from one location to the other.

^* Invited Symposium V “Platelets: Intravascular Control Mechanisms” presented to VIth International Congress on Thrombosis and Haemostasis, philadelphia, U. S. A. June 1977

• References

• 1 Bills TK, Smith JB, Silver MJ. 1976; Metabolism of (¹⁴C) arachidonic acid by human platelets. Biochimica Biophysica Acta 424: 303
• 2 Bills TK, Smith JB, Silver MJ. 1977. Platelet uptake, release and oxidation of (¹⁴C) arachidonic acid. In: Silver MJ, Smith JB, Kocsis JJ. (Eds.) Prostaglandins in Hematology. Spectrum Publishers; New York: p 27
• 3 Feinstein MB, Fiekers J, Fraser C. 1976; An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. Journal of Pharmacology and Experimental Therapeutics 197: 215
• 4 Gerrard JM, White JG. 1976; The structure and function of platelets with emphasis on their contractile nature. Pathobiology Annual 6: 31
• 5 Gerrard JM, White JG, Rao GH R, Townsend D. 1976; a Localization of platelet prostaglandin production in the platelet dense tubular system. American Journal of Pathology 83: 283
• 6 Gerrard JM, Peterson DA, Townsend A, White JG. 1976; b Prostaglandins and platelet contraction. Circulation Supp (Suppl. 02) 196
• 7 Gerrard JM, Townsend D, Stoddard S, Witkop jr CJ, White JG. 1977; a The influence of prostaglandin G₂on platelet ultrastructure and platelet secretion. American Journal of Pathology 86: 99
• 8 Gerrard JM, Peller J, Krick T, White JG. 1977; b Cyclic AMP and platelet prostaglandin synthesis. Prostaglandins 14: 39
• 9 Moncada S, Needleman P, Bunting S, Vane JR. 1976; Prostaglandin endoperoxide and thromboxane generating systems and their selective inhibition. Prostaglandins 12: 323
• 10 Oelz O, Knapp HR, Roberts LJ, Sweetman BJ, Oates JA, Reed PW. 1977; Calcium ionophore stimulated thromboxane and prostaglandin formation by platelets. Prostaglandins 13: 1013
• 11 Pickett WC, Jesse RL, Cohen P. 1977; Initiation of phospholipase A₂activity in human platelets by the calcium ionophore A23187. Biochimica Biophysica Acta 486: 209
• 12 Rittenhouse-Simmons S, Deykin D. 1977; The mobilization of arachidonic acid in platelets exposed to thrombin or ionophore A23187. Journal of Clinical Investigation 60: 495
• 13 Siekevitz P. 1970; The organization of biological membranes. New England Journal of Medicine 283: 1035
• 14 White JG. 1972; Interaction of membrane systems in blood platelets. American Journal of Pathology 66: 295
• 15 White JG, Rao GH R, Gerrard JM. 1974; Effects of the ionophore A23187 on blood platelets II. Influence on ultrastructure. American Journal of Pathology 77: 135