BIOMAT Database Logo BIOMAT Database Logo

Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine. 2001

B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan.

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007700 Kinetics The rate dynamics in chemical or physical systems.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D011760 Pyrrolidinones A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed) Pyrrolidinone,Pyrrolidone,Pyrrolidones
D004110 Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions. Aldizem,CRD-401,Cardil,Cardizem,Dilacor,Dilacor XR,Dilren,Diltiazem Hydrochloride,Diltiazem Malate,Dilzem,Tiazac,CRD 401,CRD401
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004963 Estrenes Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds. 19-Norandrostenes,19 Norandrostenes

Related Publications

B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Calcium-dependent synergistic interaction of platelet activating factor and epinephrine in human platelet aggregation.
January 2003, Acta pharmacologica Sinica,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Biochemical mechanisms in 5-hydroxytryptamine-induced human platelet aggregation.
December 1985, Agents and actions,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
The molecular mechanisms involved in lectin-induced human platelet aggregation.
November 2017, Biological chemistry,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
5-hydroxytryptamine and platelet aggregation.
February 1983, Federation proceedings,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Mechanisms of platelet activating factor-induced aggregation and secretion in human platelets.
January 1990, Prostaglandins,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Histamine potentiates human platelet aggregation induced by platelet-activating factor.
January 1992, International archives of allergy and immunology,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Xanthines inhibit human platelet aggregation induced by platelet-activating factor.
August 1992, Clinical and experimental pharmacology & physiology,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Letter: Aggregation of human platelets by platelet-activating factor.
February 1975, Lancet (London, England),
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation.
June 2004, Experimental & molecular medicine,
B H Shah, and H Rasheed, and I H Rahman, and A H Shariff, and F L Khan, and H B Rahman, and S Hanif, and S A Saeed
Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists.
January 2015, Drug design, development and therapy,
Copied contents to your clipboard!