Inhibitory effects of pentamidine on N-methyl-D-aspartate (NMDA) receptor/channels in the rat brain.
Effects of pentamidine, a therapeutic drug for Pneumocystis carinii pneumonia (PCP) in acquired immunodeficiency syndrome (AIDS), on specific bindings of [3H](+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,11-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), or FK-506 or cyclosporin A (immunosuppressants). 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 Ca(2+)-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.
Kitamura
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Arima
T
T
Sato
T
T
Nakamura
J
J
Nomura
Y
Y
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009568:Nitrendipine / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010419:Pentamidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000008:administration & dosage; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013096:Spermine / Q000494:pharmacology; D014981:Xenopus
D000998:Antiviral Agents; D015220:Calcium Channels; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D010419:Pentamidine; D016291:Dizocilpine Maleate; D009568:Nitrendipine; D005998:Glycine