This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McNicol, A. Articles by Drouin, J. Search for Related Content PubMed PubMed Citation Articles by McNicol, A. Articles by Drouin, J.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:628-632.)
© 1996 American Heart Association, Inc.

Articles

Defective Thrombin-Induced Calcium Changes and Aggregation of Bernard-Soulier Platelets Are Not Associated With Deficient Moderate-Affinity Receptors

A. McNicol; M. Sutherland; R. Zou; J. Drouin

From the Departments of Oral Biology and Pharmacology, University of Manitoba, Winnipeg, Manitoba (A.M.), and the Departments of Laboratory Medicine (M.S.) and Medicine (R.Z., J.D.), University of Ottawa, Ottawa, Ontario, Canada.

Correspondence to Dr A. McNicol, Department of Oral Biology, University of Manitoba, 780 Bannatyne Ave, Winnipeg, Manitoba, R3E 0W2, Canada. E-mail mcnic@bldghsc.lan1.umanitoba.ca.

Abstract Cloning of the moderate-affinity, serpentine thrombin receptor has helped clarify the mechanism of thrombin-induced platelet activation. Proteolytic cleavage by thrombin generates a new amino terminal that autostimulates the receptor, leading to activation of multiple signaling pathways and the platelet response. The function of other thrombin receptors, such as high-affinity glycoprotein Ib (GPIb), on platelets and their relationships to the moderate-affinity receptor remain unclear. The present study examined the role of the moderate-affinity thrombin receptor in Bernard-Soulier syndrome (BSS) platelets, which contain low amounts of GPIb. Platelets from four BSS subjects displayed normal aggregation profiles and cytosolic calcium changes in response to moderate or high concentrations of thrombin. In contrast, the BSS platelet aggregation response was delayed and calcium changes were absent in response to low thrombin concentrations. Platelets from an asymptomatic BSS heterozygote displayed an activation profile similar to those of control individuals. Specific activation of the moderate-affinity receptor by a synthetic peptide caused similar aggregation in platelets from all individuals. The synthetic peptide also elicited calcium responses in BSS platelets. Platelets from the BSS subjects and from an individual with the May-Hegglin anomaly showed increased expression of the moderate-affinity thrombin receptor by flow-cytometric analyses. These results suggest that BSS platelets possess high levels of a functional moderate-affinity thrombin receptor, probably due to large platelet size, and provide indirect evidence that a high-affinity thrombin receptor is associated with GPIb.

Key Words: platelets • thrombin • TRAP • calcium • Bernard-Soulier syndrome

This article has been cited by other articles:

				J. F.W. Keuren, S. J.H. Wielders, H. Ulrichts, T. Hackeng, J. W.M. Heemskerk, H. Deckmyn, E. M. Bevers, and T. Lindhout Synergistic Effect of Thrombin on Collagen-Induced Platelet Procoagulant Activity Is Mediated Through Protease-Activated Receptor-1 Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1499 - 1505. [Abstract] [Full Text] [PDF]

				J. S. Mruk, M. W. I. Webster, M. Heras, J. M. Reid, D. E. Grill, and J. H. Chesebro Flavone-8-Acetic Acid (Flavonoid) Profoundly Reduces Platelet-Dependent Thrombosis and Vasoconstriction After Deep Arterial Injury In Vivo Circulation, January 25, 2000; 101(3): 324 - 328. [Abstract] [Full Text] [PDF]

				A. McNicol and C. A. Robson Thrombin Receptor-Activating Peptide Releases Arachidonic Acid from Human Platelets: A Comparison with Thrombin and Trypsin J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 861 - 867. [Abstract] [Full Text]