Acute membrane effects of trimetazidine in human platelets.
The mechanisms by which trimetazidine (1-[2,3,4-trimethoxybenzyl]-piperazine) exerts its cytoprotective action have not been identified. This study was designed to investigate in human platelets and erythrocyte ghosts a possible perturbation of membrane dynamics by trimetazidine. Its effects on the steady-state anisotropies of two fluorescent probes, trimethylamino-diphenyl-hexatriene (TMA-DPH) and diphenylhexatriene (DPH) were compared. The effects on the aggregatory responses to collagen and ADP, and on platelet cAMP content were also investigated. In platelets, trimetazidine dose-dependently raised TMA-DPH anisotropy but not that of DPH. It reduced cAMP content (in the presence of Ro 15-2041, a phosphodiesterase inhibitor) and the aggregation responses to collagen and ADP. This suggests that trimetazidine decreases the 'fluidity' of the outer part of the plasma membrane, the adenylyl cyclase activity and some steps involved in platelet activation. In erythrocyte ghosts, the fluorescence anisotropy of TMA-DPH was not modified by trimetazidine. The membrane effects reported here could participate in the protection of cell metabolism afforded by a long-term treatment with trimetazidine.
CNRS URA 1482, Necker Medical School, Paris, France.
M A
MA
Devynck
K H
KH
Le Quan Sang
Y
Y
Joulin
M
M
Mazeaud
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D004161:Diphenylhexatriene; D004910:Erythrocyte Membrane / Q000187:drug effects; D005454:Fluorescence Polarization; D006801:Humans; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D014292:Trimetazidine / Q000494:pharmacology*
D004161:Diphenylhexatriene; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D014292:Trimetazidine