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Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets.
Am J Physiol. 1985 Jul; 249(1 Pt 2):H8-13.AJ

Abstract

We previously demonstrated that thromboxane A2 and/or prostaglandin H2 (TXA2/PGH2), ADP, and A23187 cause calcium mobilization in intact human platelets. Other studies have also shown that platelet shape change and aggregation induced by a variety of platelet agonists can be reversed by specific antagonists. In the present study, we used the fluorescent calcium probe chlortetracycline to evaluate whether the reversal of platelet activation involves a resequestration of intraplatelet calcium. It was found that the TXA2/PGH2 receptor antagonist 13-azaprostanoic acid (13-APA) reversed calcium mobilization and shape change induced by AA but not that induced by ADP. A similar specificity of action was observed using the specific ADP receptor antagonist, ATP, in that ATP only reversed ADP-induced calcium release and shape change. In contrast, prostacyclin reversed both AA and ADP-induced calcium redistribution and shape change. In the latter experiments, a net calcium sequestration was actually observed on prostacyclin addition. These findings indicate that the resequestration of released calcium leads to platelet deactivation. Furthermore, there appear to be at least two mechanisms by which a reduction in cytosolic calcium can be produced: specific interruption of the agonist-receptor interaction, for example, 13-APA antagonism of TXA2/PGH2; and stimulation of platelet adenosine 3',5'-cyclic monophosphate production by prostacyclin and consequent calcium sequestration.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2409821

Citation

Brace, L D., et al. "Reversal of Thromboxane A2/prostaglandin H2 and ADP-induced Calcium Release in Intact Platelets." The American Journal of Physiology, vol. 249, no. 1 Pt 2, 1985, pp. H8-13.
Brace LD, Venton DL, Le Breton GC. Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets. Am J Physiol. 1985;249(1 Pt 2):H8-13.
Brace, L. D., Venton, D. L., & Le Breton, G. C. (1985). Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets. The American Journal of Physiology, 249(1 Pt 2), H8-13.
Brace LD, Venton DL, Le Breton GC. Reversal of Thromboxane A2/prostaglandin H2 and ADP-induced Calcium Release in Intact Platelets. Am J Physiol. 1985;249(1 Pt 2):H8-13. PubMed PMID: 2409821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets. AU - Brace,L D, AU - Venton,D L, AU - Le Breton,G C, PY - 1985/7/1/pubmed PY - 1985/7/1/medline PY - 1985/7/1/entrez SP - H8 EP - 13 JF - The American journal of physiology JO - Am J Physiol VL - 249 IS - 1 Pt 2 N2 - We previously demonstrated that thromboxane A2 and/or prostaglandin H2 (TXA2/PGH2), ADP, and A23187 cause calcium mobilization in intact human platelets. Other studies have also shown that platelet shape change and aggregation induced by a variety of platelet agonists can be reversed by specific antagonists. In the present study, we used the fluorescent calcium probe chlortetracycline to evaluate whether the reversal of platelet activation involves a resequestration of intraplatelet calcium. It was found that the TXA2/PGH2 receptor antagonist 13-azaprostanoic acid (13-APA) reversed calcium mobilization and shape change induced by AA but not that induced by ADP. A similar specificity of action was observed using the specific ADP receptor antagonist, ATP, in that ATP only reversed ADP-induced calcium release and shape change. In contrast, prostacyclin reversed both AA and ADP-induced calcium redistribution and shape change. In the latter experiments, a net calcium sequestration was actually observed on prostacyclin addition. These findings indicate that the resequestration of released calcium leads to platelet deactivation. Furthermore, there appear to be at least two mechanisms by which a reduction in cytosolic calcium can be produced: specific interruption of the agonist-receptor interaction, for example, 13-APA antagonism of TXA2/PGH2; and stimulation of platelet adenosine 3',5'-cyclic monophosphate production by prostacyclin and consequent calcium sequestration. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/2409821/Reversal_of_thromboxane_A2/prostaglandin_H2_and_ADP_induced_calcium_release_in_intact_platelets_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.1985.249.1.H8?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -