Enhanced epinephrine-induced platelet aggregation in individuals carrying the G protein beta3 subunit 825T allele

FEBS Lett. 2000 Nov 10;484(3):199-201. doi: 10.1016/s0014-5793(00)02158-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Adenylate Cyclase Toxin*
  • Adolescent
  • Adult
  • Alleles
  • Colforsin / pharmacology
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Synergism
  • Epinephrine / pharmacology*
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Humans
  • In Vitro Techniques
  • Isoenzymes / blood
  • Male
  • Membrane Proteins
  • P-Selectin / blood
  • Pertussis Toxin*
  • Platelet Aggregation / genetics
  • Platelet Aggregation / physiology*
  • Polymorphism, Genetic*
  • Prostaglandin-Endoperoxide Synthases / blood
  • Thrombin / pharmacology
  • Vasopressins / pharmacology
  • Virulence Factors, Bordetella / pharmacology*

Substances

  • Adenylate Cyclase Toxin
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • P-Selectin
  • Virulence Factors, Bordetella
  • Vasopressins
  • Colforsin
  • Adenosine Diphosphate
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Pertussis Toxin
  • Thrombin
  • Heterotrimeric GTP-Binding Proteins
  • Epinephrine