title: Mepacrine-induced inhibition of the inward current mediated by 5-HT3 receptors in rat nodose ganglion neurones.
abstract: 1. With the whole-cell patch clamp technique, the effect of the antimalarial drug, mepacrine (quinacrine) on the inward current mediated by 5-HT3 receptors (5-hydroxytryptamine (5-HT)-induced current) was investigated in isolated nodose ganglion neurones of the rat. 2. 5-HT and the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide elicited an inward current which reversed at around 0 mV and quickly desensitized to a steady state level. 3. Mepacrine dose-dependently inhibited the peak current induced by 5-HT with an IC50 of 2.1 microM and an apparent Hill coefficient of 0.99. 4. Mepacrine increased the decay rate of the 5-HT-induced current. 5. The effect of mepacrine on the 5-HT-induced current was reversible and not dependent on membrane potential. The reversal potential of the 5-HT-induced current was not affected. 6. Intracellular mepacrine had no significant effect on the 5-HT-induced current and did not block the extracellular action of mepacrine. 7. Concentration-response curves in the presence and absence of mepacrine suggest a non-competitive inhibition of 5-HT-induced current by mepacrine.
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
authors.forename: P
authors.initials: P
authors.lastname: Fan
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D010741:Phospholipases A; D011796:Quinacrine