Inhibitory Effects of Pentamidine on N-Methyl-D-aspartate (NMDA) Receptor/Channels in the Rat Brain

摘要

Effects of pentamidine, a therapeutic drug for Pneumocystis carinii pneumonia (PCP) in acquired im-munodeficiency syndrome (AIDS), on specific bindings of [3H](+)-5-methyl-10,ll-dihydro-5H-dibenzo[a,p]cycIo-hepten-5,ll-imine maleate (MK-801) and [3H]nitrendipine were investigated in crude synaptic membranes (CSM) of rat brain. Pentamidine inhibited [3H]MK-801 binding but did not change [3H]nitrendipine binding, although neither binding was inhibited by 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxycytidine (inhibitors for reverse transcriptase of HIV-1),1 or FK-506 or cyclosporin A (hnmunosuppressants). In Triton X-100-treated CSM (post-synaptic density-rich fractions), the inhibitory effect of pentamidine on [3H]MK-801 binding was partially prevented by addition of spermine and NMDA plus glycine (Gly). Electrophysiological experiments showed that pentamidine also inhibited Ca2+-current evoked by NMDA plus Gly in Xenopus oocytes injected with rat brain mRNA. These results suggest that pentamidine is a potent inhibitor for NMDA receptor/channels.