The platelet rebound phenomenon during PGI2-infusion occurs at the receptor level.
In 6 patients treated with continuous prostaglandin I2 (PGI2)-infusion using a portable pump at a rate of 5 ng/kg/min for 7 days drug receptor interaction of [3H]Iloprost, a stable PGI2 analogue, with a particulate platelet membrane fraction was investigated. Saturation binding experiments of the high affinity platelet prostacyclin receptor performed before and at the end of PGI2 infusion revealed a significant increase of dissociation constant (Kd) and increase in maximal number of binding sites (Bmax). These findings suggest that continuous long-term PGI2 infusion results in a functional desensitization of the membrane-bound PGI2 platelet receptor with a decrease in receptor affinity and an increase in number of binding sites as suggested earlier based upon platelet sensitivity behaviour.
Steurer
G
G
II. Department of Internal Medicine, University of Vienna, Austria.
Fitscha
P
P
Sinzinger
H
H
D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D011982:Receptors, Prostaglandin / Q000187:drug effects*
D011982:Receptors, Prostaglandin; D011464:Epoprostenol