Inhibition by bis(7)-tacrine of 5-HT-activated current in rat TG neurons.
Whole-cell recordings were performed on rat trigeminal ganglion (TG) neurons as a modeling experiment to investigate the effect of bis (7)-tacrine, a potential anti-Alzheimer's disease (AD) drug, on 5-HT-induced current (I5-HT). Extracellular 5-HT activated a concentration-dependent inward current that was blocked by ICS 205930. Co-application of bis(7)-tacrine inhibited I5-HT markedly with IC50 at 2 x 10 M. Bis(7)-tacrine shifted the concentration-response curve for I5-HT rightwards with its maximum response unchanged and EC50 increased, suggesting that this inhibition was competitive in nature. Intracellular dialysis of GDP-beta-S did not block bis(7)-tacrine inhibition of I5-HT, which excluded the involvement of G-protein mediation. These results may offer possible modality to understanding the anti-AD mechanism of bis(7)-tacrine.
Luo
Jia-Lie
JL
Department of Molecular and Cellular Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China.
Zhang
Jian
J
Guan
Bing-Cai
BC
Pang
Yuan-Ping
YP
Han
Yi-Fan
YF
Li
Zhi-Wang
ZW
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D012701:Serotonin; D013619:Tacrine; C023427:guanosine 5'-O-(2-thiodiphosphate); D019204:GTP-Binding Proteins