Impaired responsiveness of platelets to epinephrine due to α2A adrenoreceptor deficiency in Male Chinese

Platelets. 2016;27(2):149-54. doi: 10.3109/09537104.2015.1049137. Epub 2015 Jun 17.

Abstract

Epinephrine is known as a weak, but important, agonist for platelet activation. It has been reported that the responsiveness of platelets to epinephrine was markedly impaired in 6% of Caucasians and in 16% of Japanese. The purpose of this study was to screen and characterize this abnormality in healthy Taiwanese Chinese volunteers. We used aggregometry, flow cytometry and platelet function analyzer (PFA)-100 system to assess in 50 healthy male volunteers the responsiveness of platelets to epinephrine stimulation. Using α2A adrenoceptor antagonist BRL44408 maleate competition and a [(3)H]yohimbin binding assay, we evaluated α2A adrenoceptors on platelets. The aggregation of platelets after stimulation with 10 μM of epinephrine indicated two distinct groups of study participants: 24 (48.0%) good- and 26 (52.0%) impaired-responders to epinephrine. Flow cytometric analysis of platelets after stimulated with 1 μM epinephrine showed that glycoprotein (GP) IIb/IIIa and P-selectin expression of epinephrine good- and impaired-responders were 27.1 ± 11.0% vs. 9.9 ± 5.4% (p = 0.003) and 12.2 ± 6.2% vs. 3.6 ± 3.5% (p < 0.001), respectively. The PFA-100 system showed that epinephrine-impaired-responders had a longer collagen-epinephrine induced closure time. Good-responder platelets incubated with BRL44408 maleate had an impaired response to epinephrine stimulation. [(3)H]yohimbine binding studies showed fewer α2A adrenoreceptors on the platelets of epinephrine-impaired-responders than on those of good-responders. The prevalence of impaired responsiveness to epinephrine was high and probably due to α2A adrenoreceptor deficiency in male Taiwanese Chinese.

Keywords: epinephrine; flow cytometry; platelet aggregometry; α2A adrenoreceptor.

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adrenergic alpha-2 Receptor Antagonists / pharmacology*
  • Adult
  • Asian People
  • Biological Assay
  • Biological Transport
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Collagen / pharmacology
  • Epinephrine / pharmacology*
  • Gene Expression
  • Humans
  • Male
  • Maleates / pharmacology*
  • P-Selectin / blood
  • P-Selectin / genetics
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Receptors, Adrenergic, alpha-2 / deficiency*
  • Receptors, Adrenergic, alpha-2 / genetics
  • Tritium
  • Yohimbine / metabolism

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Maleates
  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Adrenergic, alpha-2
  • Tritium
  • Yohimbine
  • Collagen
  • Epinephrine