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Related Experiment Videos

Interaction between platelet receptor and iloprost isomers.

A L Tsai1, H Vijjeswarapu, K K Wu

  • 1Department of Internal Medicine, University of Texas Health Science Center, Houston 77225.

Biochimica Et Biophysica Acta
|July 21, 1988
PubMed
Summary

The 16(S) iloprost isomer is significantly more potent than the 16(R) isomer in inhibiting platelet aggregation and exhibits distinct receptor binding characteristics. This difference is attributed to the molecule's orientation within the prostacyclin receptor channel.

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Area of Science:

  • Pharmacology
  • Biochemistry
  • Molecular Biology

Background:

  • Iloprost, a prostacyclin analog, is used to study interactions with platelets and vascular cells.
  • Iloprost is typically supplied as a mixture of 16(S) and 16(R) stereoisomers.

Purpose of the Study:

  • To compare the biological activity and platelet receptor binding of iloprost stereoisomers.
  • To elucidate the structural basis for differential isomer activity.

Main Methods:

  • Assessing inhibition of collagen-induced platelet aggregation.
  • Quantifying equilibrium receptor binding using rapid filtration.
  • Measuring association rates of iloprost isomers to platelet membrane receptors.

Main Results:

Related Experiment Videos

  • The 16(S) isomer demonstrated 20-fold greater potency in inhibiting platelet aggregation compared to the 16(R) isomer.
  • 16(S) isomer showed higher affinity (Kd 13.4 nM) and capacity (Bmax 665 fmol/mg) for platelet receptors than the 16(R) isomer (Kd 288 nM, Bmax 425 fmol/mg).
  • The 16(S) isomer exhibited a significantly faster association rate (0.036 s-1) than the 16(R) isomer (0.001 s-1).

Conclusions:

  • Stereoisomer-specific differences in iloprost's biological activity and receptor binding are substantial.
  • Favorable molecular orientation of the 16(S) isomer in the receptor channel likely explains its enhanced binding and activity.
  • Iloprost isomers should be treated as distinct compounds in prostacyclin receptor binding studies.