Effect of calcium and calcium antagonists on [3H]-Paf-acether binding to washed human platelets

Thromb Res. 1986 Jan 15;41(2):251-62. doi: 10.1016/0049-3848(86)90233-1.

Abstract

[3H]-Platelet activating factor (Paf-acether, 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) binds to washed human platelets in a specific, dose-dependent, and saturable manner. Scatchard analysis reveals a high affinity site with a KD value of 0.25 +/- 0.033 nM (245 +/- 30 sites per platelet), and a second low affinity site with a KD value of 9.22 +/- 1.17 nM (1616 +/- 165 sites per platelet). Binding to the high affinity site is independent of buffer calcium concentration, inhibited on an equimolar basis by unlabelled 1-O-octadecyl-Paf-acether, but remains unchanged in the presence of 1-O-octadecyl-lyso-Paf-acether. The relative inhibitory effect of four calcium antagonists on [3H]-Paf-acether high affinity binding correlates closely with their respective anti-aggregatory activity against Paf-acether induced responses in human PRP; order of potency being (+)-cis diltiazem greater than (+/-)-verapamil greater than (-)-cis diltiazem greater than nifedipine. In the case of (+)-cis diltiazem, the effect is competitive, stereo-specific and progressively reversed by addition of calcium (1.0 mM and 5.0 mM). A close spatial relationship may thus exist between the Paf-acether receptor and membrane calcium channels in the human platelet.

MeSH terms

  • Benzazepines / pharmacology*
  • Blood Platelets / metabolism*
  • Buffers
  • Calcium / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Diltiazem / pharmacology*
  • Humans
  • Male
  • Nifedipine / pharmacology*
  • Platelet Activating Factor / metabolism*
  • Platelet Aggregation / drug effects
  • Statistics as Topic
  • Stereoisomerism
  • Tritium
  • Verapamil / pharmacology*

Substances

  • Benzazepines
  • Buffers
  • Calcium Channel Blockers
  • Platelet Activating Factor
  • Tritium
  • Verapamil
  • Diltiazem
  • Nifedipine
  • Calcium