Enhanced epinephrine-induced platelet aggregation in individuals carrying the G protein beta3 subunit 825T allele.
The 825T allele of a common C825T polymorphism in the gene encoding the beta3 subunit of heterotrimeric G proteins is associated with enhanced activation of pertussis toxin (PTX)-sensitive G proteins. We investigated responses of human platelets upon stimulation with epinephrine, which activates PTX-sensitive G proteins, and with agonists which activate additionally, or exclusively PTX-insensitive pathways. Slopes and maximum of the secondary aggregation were significantly enhanced in platelets from 825T allele carriers after epinephrine, and after combined epinephrine/ADP. This effect was more pronounced after inhibition of the cyclooxygenase-2 pathway by acetylsalicylic acid. This phenomenon appeared independent of platelet secretion, or inhibition of the adenylyl cyclase.
Naber
C
C
abteilung für Kardiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Germany. christoph.naber@uni-essen.de
Hermann
B L
BL
Vietzke
D
D
Altmann
C
C
Haude
M
M
Mann
K
K
Rosskopf
D
D
Siffert
W
W
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000293:Adolescent; D000328:Adult; D000483:Alleles; D005576:Colforsin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008565:Membrane Proteins; D019007:P-Selectin / Q000097:blood; D037342:Pertussis Toxin; D010974:Platelet Aggregation / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D013917:Thrombin / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D019007:P-Selectin; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D005576:Colforsin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D037342:Pertussis Toxin; D013917:Thrombin; D020962:Heterotrimeric GTP-Binding Proteins; D004837:Epinephrine