Nuciferine Relaxes Tracheal Rings via the Blockade of VDLCC and NSCC Channels

Abstract

This study aimed to elucidate the mechanisms of nuciferine (a main aporphine alkaloid of lotus leaf extract), which can induce relaxation in contracted tracheal rings. Under Ca²⁺-free and 2 mM Ca²⁺ conditions, we found that nuciferine had no effect on the resting muscle tone of tracheal rings. In contrast, nuciferine relaxed high K⁺-contracted mouse tracheal rings in a dose-dependent manner and inhibited both Ca²⁺ influx and voltage-dependent L-type Ca²⁺ channel currents induced by high K⁺. Similarly, nuciferine also inhibited acetylcholine-induced contractions in mouse tracheal rings in a dose-dependent manner. Meanwhile, both acetylcholine-induced intracellular Ca²⁺ influx and whole-cell currents of nonselective cation channels were blocked by nuciferine. Together, the results indicate that nuciferine-induced relaxation in tracheal rings mainly occurred due to the inhibition of extracellular Ca²⁺ influx through the blockade of voltage-dependent L-type Ca²⁺ channels and/or nonselective cation channels. These results suggest that nuciferine has a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm.