Potassium 2-(1-hydroxypentyl)-benzoate inhibits ADP-induced rat platelet aggregation through P2Y1-PLC signaling pathways

Naunyn-Schmiedeberg's Archives of Pharmacology
Hongyan YangXiaoliang Wang

Abstract

Potassium 2-(1-hydroxypenty1)-benzoate (dl-PHPB) is a new drug candidate for treatment of ischemic stroke with antiplatelet effect. In this study, we investigated the mechanisms of dl-PHPB in inhibiting platelet aggregation. The ADP-activated P2Y1-Gq-PLC and P2Y12-Gi-AC pathways were observed, respectively. Intravenous injection of dl-PHPB (1.3, 3.9, 12.9 mg/kg) significantly inhibited ADP-, collagen-, and arachidonic acid-induced rat platelet aggregation in a dose-dependent manner, and dl-PHPB had a relatively more potent inhibitory effect on ADP-induced rat platelet aggregation than other agonists. Dl-PHPB also showed a decreased expression of CD62P (a marker for platelet activation) mediated by ADP. Both dl-PHPB and ticlopidine (P2Y12 receptor antagonist) decreased cytoplasmic Ca(2+) concentration. But, dl-PHPB did not reverse the inhibition of PGE1-induced platelet cAMP formation by ADP, which was different from ticlopidine. Further, dl-PHPB instead of ticlopidine showed increasing phospholipase C-β phosphorylation (ser(1105)). The m-3M3FBS, a phospholipase C activator, attenuated the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation and enhanced IP1 accumulation in rat platelets. Dl-PHPB decreased IP1 accumu...Continue Reading

References

Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·J Jin, S P Kunapuli
Jul 13, 2000·The Journal of Biological Chemistry·C YueB M Sanborn
Apr 16, 2003·Molecular Pharmacology·Yoe-Sik BaeSung Ho Ryu
Oct 8, 2003·Current Pharmaceutical Design·Satya P KunapuliTodd M Quinton
Aug 11, 2004·British Journal of Pharmacology·Jelena KrjukovaJyrki P Kukkonen
Jul 7, 2005·American Journal of Physiology. Renal Physiology·Helena FreckerCatharine Whiteside
Mar 11, 2006·The Journal of Pharmacology and Experimental Therapeutics·Yi ZhangXiao-Liang Wang
Dec 13, 2006·Circulation Research·Stefan Offermanns
Feb 15, 2007·The Biochemical Journal·Analia GarciaSatya P Kunapuli
Jul 17, 2007·Cytometry. Part B, Clinical Cytometry·Silverio SbranaAldo Clerico
Dec 14, 2007·The New England Journal of Medicine·Giovanni Davì, Carlo Patrono
Nov 9, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·David Stegner, Bernhard Nieswandt
Mar 24, 2011·Journal of Atherosclerosis and Thrombosis·Masafumi UenoDominick Joseph Angiolillo
May 13, 2011·Journal of Thrombosis and Thrombolysis·Gaurav Sharma, Jeffrey S Berger
Jul 14, 2011·Nature Reviews. Cardiology·Omair Yousuf, Deepak L Bhatt
Nov 1, 2011·Thrombosis Research·Nicoleta AlexandruAdriana Georgescu
Sep 12, 2012·Cardiovascular & Hematological Agents in Medicinal Chemistry·Gioel Gabrio SeccoAndrea Rognoni
Mar 15, 2013·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Alicja WasilukRobert Milewski

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.