guanosine-diphosphate and Alzheimer-Disease

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.

Topics: Alzheimer Disease; Animals; Cell Membrane; Cells, Cultured; Dose-Response Relationship, Drug; Drug Interactions; GTP-Binding Proteins; Guanosine Diphosphate; Membrane Potentials; Neural Inhibition; Neurons; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Synaptic Transmission; Tacrine; Thionucleotides; Trigeminal Ganglion