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Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides.
J Lab Clin Med. 1985 Sep; 106(3):246-52.JL

Abstract

Increase in thromboxane A2 (TXA2) generation has been proposed as a mechanism of dynamic vaso-occlusion and in vivo platelet thrombus formation. We have examined the effects of CGS-13080, an imidazole derivative, on rabbit and human TXA2-prostacyclin (PGI2) "balance." In rabbits given CGS-13080, serum levels of TXB2 (stable metabolite of TXA2) were inhibited 81% at 2 hours and 56% at 24 hours (both P less than or equal to 0.01). Collagen-induced platelet aggregation was inhibited at 2 hours after CGS-13080 administration. In contrast, serum levels of 6-keto-PGF1 alpha (stable hydrolysis product of PGI2) increased 587% compared with control values at 2 hours (P less than or equal to 0.01). Platelet and white blood cell counts were not significantly altered. In human blood incubated in vitro with CGS-13080, serum TXB2 was completely inhibited, whereas PGI2 generation was stimulated (both P less than or equal to 0.001). In other experiments, we demonstrated uptake of platelet-generated cyclic endoperoxides by leukocytes and generation of PGI2 in the presence of CGS-13080 but not indomethacin. Thus, CGS-13080 inhibits TXA2 and stimulates PGI2 production in rabbit and human blood. Increase in PGI2 generation with TXA2 inhibition may be of potential benefit in conditions characterized by platelet hyperactivity.

Authors

Mehta J
No affiliation info available
Mehta P
No affiliation info available
Lawson DL
No affiliation info available
Ostrowski N
No affiliation info available
Brigmon L
No affiliation info available

MeSH

6-Ketoprostaglandin F1 alphaAnimalsBlood PlateletsCalcimycinCalcium ChlorideCollagenEpoprostenolImidazolesIndomethacinLeukocytesOxidoreductasesPlatelet AggregationPyridinesRabbitsThromboxane A2Thromboxane B2Thromboxane-A SynthaseThromboxanes

Pub Type(s)

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

Language

eng

PubMed ID

3928780

Citation

Mehta, J, et al. "Influence of Selective Thromboxane Synthetase Blocker CGS-13080 On Thromboxane and Prostacyclin Biosynthesis in Whole Blood: Evidence for Synthesis of Prostacyclin By Leukocytes From Platelet-derived Endoperoxides." The Journal of Laboratory and Clinical Medicine, vol. 106, no. 3, 1985, pp. 246-52.
Mehta J, Mehta P, Lawson DL, et al. Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides. J Lab Clin Med. 1985;106(3):246-52.
Mehta, J., Mehta, P., Lawson, D. L., Ostrowski, N., & Brigmon, L. (1985). Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides. The Journal of Laboratory and Clinical Medicine, 106(3), 246-52.
Mehta J, et al. Influence of Selective Thromboxane Synthetase Blocker CGS-13080 On Thromboxane and Prostacyclin Biosynthesis in Whole Blood: Evidence for Synthesis of Prostacyclin By Leukocytes From Platelet-derived Endoperoxides. J Lab Clin Med. 1985;106(3):246-52. PubMed PMID: 3928780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides. AU - Mehta,J, AU - Mehta,P, AU - Lawson,D L, AU - Ostrowski,N, AU - Brigmon,L, PY - 1985/9/1/pubmed PY - 1985/9/1/medline PY - 1985/9/1/entrez SP - 246 EP - 52 JF - The Journal of laboratory and clinical medicine JO - J Lab Clin Med VL - 106 IS - 3 N2 - Increase in thromboxane A2 (TXA2) generation has been proposed as a mechanism of dynamic vaso-occlusion and in vivo platelet thrombus formation. We have examined the effects of CGS-13080, an imidazole derivative, on rabbit and human TXA2-prostacyclin (PGI2) "balance." In rabbits given CGS-13080, serum levels of TXB2 (stable metabolite of TXA2) were inhibited 81% at 2 hours and 56% at 24 hours (both P less than or equal to 0.01). Collagen-induced platelet aggregation was inhibited at 2 hours after CGS-13080 administration. In contrast, serum levels of 6-keto-PGF1 alpha (stable hydrolysis product of PGI2) increased 587% compared with control values at 2 hours (P less than or equal to 0.01). Platelet and white blood cell counts were not significantly altered. In human blood incubated in vitro with CGS-13080, serum TXB2 was completely inhibited, whereas PGI2 generation was stimulated (both P less than or equal to 0.001). In other experiments, we demonstrated uptake of platelet-generated cyclic endoperoxides by leukocytes and generation of PGI2 in the presence of CGS-13080 but not indomethacin. Thus, CGS-13080 inhibits TXA2 and stimulates PGI2 production in rabbit and human blood. Increase in PGI2 generation with TXA2 inhibition may be of potential benefit in conditions characterized by platelet hyperactivity. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/3928780/Influence_of_selective_thromboxane_synthetase_blocker_CGS_13080_on_thromboxane_and_prostacyclin_biosynthesis_in_whole_blood:_evidence_for_synthesis_of_prostacyclin_by_leukocytes_from_platelet_derived_endoperoxides_ DB - PRIME DP - Unbound Medicine ER -