The Research Of Bitter Tastant On The Airway Smooth Muscle And Its Signal Pathway

Taste is very important sense of the mammals, bitter taste is one of the five basic tastes.Bitter taste receptors were widely found in many organs in humans recently, such asgastrointestinal cells, testis cells, nerve cells and airway smooth muscle cells. Recentstudies shown that bitter taste receptors are involved in the relaxation of airway smoothmuscle cells. After they give the agonist of airway smooth muscles, such as ACH lead to thecontraction of the airway smooth muscles, then they give the bitter such as chloroquine canrelax this contraction. But if they don’t give the agonist, at the rest level of the airwaysmooth muscle cells, bitter can make the cells release Ca2+.The mechanism of thisparadoxical role of bitter on airway smooth muscle cells should be clarified as soon aspoosible.One side of this paper investigate the relaxation of the airway smooth muscle, we testthe force of the airway smooth muscle, we give three times pre-contraction, then we givethe agonist of the airway ACH, by the force rise to the stable, we give the chloroquine, thenthe force drop to the rest level; we also use confocal dual-recording the transmission lightand the laser to test theCa2+, we test the fifteen cells and find that after we give the ACHlead to the cell length shorten and Ca2+rise, then give the chloroqine, the cell relaxed andCa2+reduce to the rest level. The two experiment demonstrate that choloroquine reduce theCa2+lead to the relaxation of the airway smooth muscle cells.On the other side we find that at the rest level of airway smooth muscle, how bitterlead to the contraction. We use the force to test the airway smooth muscle cell, chloroquinecan lead to a transiently contraction. To test the Ca2+from outside or inside of the cell, weinstead the calcium-free solution, chloroquine also can lead to the contraction. To furtherconfirm this,we used the Ca2+pump inhibitor CPA to deplete intracellular Ca2+store andthen observed chloroquine-induced contraction was inhibited. These two sides demonstratechloroquine-induced contraction is mediated by intracellular Ca2+store release.The chloroquine-induced contraction pattern likely results from Ca2+releasing fromintracellular Ca2+store, we observed the role of IP3receptors. Following IP3receptorsinhibitor2-APB to block IP3receptors, chloroquine-induced contraction was blocked. Thisresults suggests IP3receptors mediate chloroquine-induced contraction, and implying theupstream G protein-PLC pathway may play a role. Thus, we used selective Gα inhibitorPTX to incubate tracheal rings overnight and found this treatment completely abolishedchloroquine-induced contraction. While, similar treatment with Gβγ specific inhibitorgalleon, failed to block chloroquine-induced contraction. These data indicate thatchloroquine through Gα-PLC-IP3-IP3R pathway releases Ca2+from intracellular store and eventually causing a transient contraction.We observed that bitter through bitter taste receptors can lead to the contraction, notrelaxation. This suggests that bitter and bitter taste receptors whether play an important roleor not, in the formation of the airway hyperresponsiveness. To further treatment play a goodfoundation role.