Activity of α7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes

Nicotinic receptors containing α7 subunits are widely distributed in the central nervous system and are thought to be involved in a number of functions. However, it has been difficult to study α7-containing receptors in vivo because of a paucity of selective agonists. A new spirooxazolidinone compound, AR-R17779, was recently described as potent agonist at α7 receptors, but electrophysiological studies at other types of nicotinic receptors have not been carried out. We characterized the activity of AR-R17779 at α7, α4β2, α3β4, α3β2, α3β2α5 receptors expressed in Xenopus oocytes. In addition, since there is significant homology between nicotinic α7 and serotonin 5HT3 receptors, the activity of AR-R17779 at expressed 5HT3a receptors was also examined. Finally, actions of tropisetron and ondansetron, two 5HT3 antagonists, were explored. AR-R17779 was found to activate α7 receptors, but had no activity at other types of nicotinic receptors, and also had no activity at 5HT3a receptors. Tropisetron activated, while ondansetron acted as an antagonist, at α7 nicotinic receptors. The two 5HT3 antagonists also acted as antagonists at α4β2 and α3β4 nicotinic receptors. Thus, AR-R17779 was confirmed to be a selective nicotinic α7 receptor agonist and to be without activity at 5HT3 receptors. In contrast, the actions of tropisetron and ondansetron on nicotinic receptors were complex.