Relaxant effect of chloroquine in rat ileum: possible involvement of nitric oxide and BKCa.

Bitter perception has a particularly important role in host defence. However, to date, direct effects of bitter compounds on small intestinal motility have not been shown. This study investigated the effects of bitter compounds on the spontaneous contraction of longitudinal smooth muscle strips of rat ileum. Isolated longitudinal smooth muscle strips of rat ileum were used for tension recording in vitro. Immunofluorescence staining was used to identify the localization of TAS2R10 receptors. The spontaneous contraction of rat ileum was decreased after chloroquine administration. Other bitter compounds, such as quinine, denatonium and saccharin, exhibited similar effects. Chloroquine-induced relaxation was not blocked by tetrodotoxin, but was partially reversed by the nitric oxide synthase inhibitor L-NAME or the large conductance Ca(2+) -activated K(+) (BKCa) channel antagonist iberiotoxin. By surgically removing the small intestinal mucosa or bathing in Ca(2+) -free Krebs solution, the chloroquine-induced relaxation was largely attenuated. The immunofluorescence staining showed that TAS2R10 receptors were expressed in rat ileum. The results indicate that bitter receptor agonists induce relaxation of longitudinal smooth muscle strips of rat ileum, which is mediated by nitric oxide and BKCa channels. © 2013 Royal Pharmaceutical Society.