The role of ADP in endotoxin-induced equine platelet activation

We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high c...

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Veröffentlicht in:European journal of pharmacology 1996-11, Vol.315 (2), p.203-212
Hauptverfasser: Jarvis, Gavin E., Evans, Richard J., Heath, M.Fred
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container_title European journal of pharmacology
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creator Jarvis, Gavin E.
Evans, Richard J.
Heath, M.Fred
description We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin, ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-{3-[4-( o-chlorophenyl)-9-methyl-6 H-thieno[3,2,- f]- s-triazolo[4,3- a][1,4]diazepin-2-yl]proprionyl}-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. It is concluded that endotoxin-induced aggregation is dependent upon ADP released from platelet dense granules.
doi_str_mv 10.1016/S0014-2999(96)00637-1
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ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin, ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-{3-[4-( o-chlorophenyl)-9-methyl-6 H-thieno[3,2,- f]- s-triazolo[4,3- a][1,4]diazepin-2-yl]proprionyl}-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. 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ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin, ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-{3-[4-( o-chlorophenyl)-9-methyl-6 H-thieno[3,2,- f]- s-triazolo[4,3- a][1,4]diazepin-2-yl]proprionyl}-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. 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Blood cells</topic><topic>Blood Platelets - metabolism</topic><topic>Endotoxin</topic><topic>Endotoxins - pharmacology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Horses</topic><topic>Molecular and cellular biology</topic><topic>PAF (platelet-activating factor)</topic><topic>Platelet</topic><topic>Platelet Activating Factor - physiology</topic><topic>Platelet Activation - drug effects</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Spectrophotometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jarvis, Gavin E.</creatorcontrib><creatorcontrib>Evans, Richard J.</creatorcontrib><creatorcontrib>Heath, M.Fred</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jarvis, Gavin E.</au><au>Evans, Richard J.</au><au>Heath, M.Fred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of ADP in endotoxin-induced equine platelet activation</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1996-11-14</date><risdate>1996</risdate><volume>315</volume><issue>2</issue><spage>203</spage><epage>212</epage><pages>203-212</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin, ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-{3-[4-( o-chlorophenyl)-9-methyl-6 H-thieno[3,2,- f]- s-triazolo[4,3- a][1,4]diazepin-2-yl]proprionyl}-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. 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subjects Adenine nucleotide
Adenosine Diphosphate - metabolism
Adenosine Diphosphate - physiology
Adenosine Monophosphate - metabolism
Adenosine Triphosphate - metabolism
Animals
Apyrase - pharmacology
Biological and medical sciences
Blood coagulation. Blood cells
Blood Platelets - metabolism
Endotoxin
Endotoxins - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Horses
Molecular and cellular biology
PAF (platelet-activating factor)
Platelet
Platelet Activating Factor - physiology
Platelet Activation - drug effects
Platelet aggregation
Platelet Aggregation - drug effects
Spectrophotometry
title The role of ADP in endotoxin-induced equine platelet activation
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